Active, not recruitingNCT01896999Updated Sep 29, 2026

Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

A Phase 1/2 interventional study of Biopsy Procedure and Biospecimen Collection in Recurrent Classic Hodgkin Lymphoma and Refractory Classic Hodgkin Lymphoma, sponsored by National Cancer Institute (NCI). Active, not recruiting at 479 sites in United States. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment

Updated Sep 29, 2026Primary completion movedStudy completion movedGo to Updates ↓

Phase: Phase 1/2
Study type: Interventional
Enrollment: 146
Allocation: Randomized
Ages: 12 Years and older
Sex: All

Study summary

This phase I/II trial studies the side effects and best dose of ipilimumab and nivolumab when given together with brentuximab vedotin, and how well they work in treating patients with Hodgkin lymphoma that has returned after a period of improvement (recurrent) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. It is not known whether giving brentuximab vedotin and nivolumab with or without ipilimumab may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combinations of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) II. To evaluate the complete response (CR) rate for the regimens of brentuximab vedotin and nivolumab compared to brentuximab vedotin, ipilimumab, and nivolumab. (Phase II; adult cohort [aged >= 18 years]) III. To characterize the safety and toxicity of treatment combination in the pediatric population. (Phase II; pediatric cohort [aged 12-17 years])

SECONDARY OBJECTIVES:

I. To evaluate complete response (CR) rate, partial response (PR) rate and overall response rate (ORR), for the combinations of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) II. To evaluate the duration of remission (DOR) to these combinations and compare with the DOR achieved with the most recent prior systemic therapy. (Phase I) III. To evaluate the progression-free survival (PFS) and the overall survival (OS) in patients receiving the combination of brentuximab vedotin and ipilimumab, brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase I) IV. To evaluate the ORR, PR, and stable disease (SD) rate for the combinations of brentuximab vedotin and nivolumab and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II) V. To evaluate the DOR to these combinations and compare with the DOR achieved with the most recent prior systemic therapy. (Phase II) VI. To evaluate the 5 year PFS and OS in patients receiving the combinations of brentuximab vedotin and nivolumab and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II) VII. To further evaluate the safety and characterize the toxicity for the combinations of brentuximab vedotin and nivolumab, and brentuximab vedotin, ipilimumab, and nivolumab. (Phase II)

CORRELATIVE STUDY OBJECTIVES:

I. To evaluate the ability of these combinations to alter tumor specific T cell immunity. (Phase I) II. To evaluate the effects of these combinations on systemic immunity. (Phase I) III. To evaluate a panel of cytokine and T cell specific biomarkers from the peripheral blood as a potential immune signature of treatment response to therapy with these combinations for patients with relapsed/refractory Hodgkin lymphoma (HL). (Phase I) IV. To evaluate using gene expression profiling (GEP) a signature of response to these novel combinations of an antibody drug conjugate with immunomodulatory therapy. (Phase I) V. To evaluate the ability of these combinations to alter tumor specific T cell immunity, and circulating T cell phenotypes, in patients as a function of treatment response at multiple timepoints during therapy. (Phase II) VI. To evaluate peripheral blood cytokine profiles in responding and resistant patients at multiple timepoints during therapy. (Phase II) VII. To evaluate using GEP a signature of response versus (vs.) resistance to these novel combinations of an antibody drug conjugate with immunomodulatory therapy. (Phase II) VIII. To evaluate the influence of human gut microbiome dysbiosis on HL lymphomagenesis and the systemic immune response. (Phase II)

IMAGING CORRELATIVE STUDY OBJECTIVES:

I. To evaluate atypical response patterns with currently available response evaluation criteria. (Phase II) II. To correlate response evaluated using currently available response evaluation criteria with duration of response (PFS, event free survival [EFS], failure free survival [FFS]). (Phase II) III. To evaluate response patterns in different immunotherapy treatment schemes and correlate with historical data using chemotherapy. (Phase II) IV. To correlate imaging changes in all treatment schemes quantitatively with PFS. (Phase II)

EXPLORATORY OBJECTIVES:

I. Evaluate outcomes (CR, PFS) between patients with/without prior transplants. (Phase II) II. Evaluate outcomes (PFS, OS) between the patients who stay on treatment and do not go to transplant in both arms (the post auto and the few others who don't want transplant) vs the patients who go off for transplant. (Phase II) III. Evaluate outcomes (CR, PFS) in pediatric population (age 12 to \< 18 years of age) vs. adult population. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin, ipilimumab, and nivolumab followed by a phase II study.

PHASE I: Patients are assigned into 1 of 3 arms.

ARM I: Patients receive brentuximab vedotin intravenously (IV) over 90 minutes on day 1 of cycles 1-16 and ipilimumab IV over 30 minutes on day 1 of cycles 1-4, 8, 12, and 16. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-46. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-46, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive brentuximab vedotin IV over 30 minutes on day 1 of cycles 1-16 and nivolumab IV over 90 minutes on day 1 of cycles 1-34. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-34, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity.

All patients also undergo computed tomography (CT) or positron emission tomography (PET) scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.

After completion of phase I study treatment, patients are followed up every 3 months for 1 year, then every 6 months for 2 years. After completion of phase II study treatment, patients are followed up for 10 years.

Conditions studied

Recurrent Classic Hodgkin Lymphoma
Refractory Classic Hodgkin Lymphoma

In context

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 12 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria:

PHASE I (ARMS A, B, C, D, E, F, G, H, I, X, Y, Z)
Age >= 18 years
Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
Patients must have relapsed after first line chemotherapy; may have relapsed after autologous or allogeneic stem cell transplant, or have primary refractory disease; no upper limit for number of prior therapies; if status post allogeneic stem cell transplant, no active graft versus host disease
Patients may have received prior brentuximab vedotin, but must not have received brentuximab vedotin within 6 months prior to registration, and must not have relapsed within 6 months of receiving previous brentuximab vedotin; patients may not have received prior nivolumab or PD1/PDL1 axis agents; patients in the nivolumab/brentuximab cohorts ONLY (D, E, F, Y) may have received prior ipilimumab
Patients may have received other prior activating immunotherapies (i.e. checkpoint inhibitors), but must not have received them within 6 months prior to registration, and there must be no serious unresolved complication of therapy at the time of registration; for the purposes of this study monoclonal antibodies and antibody drug conjugates are not considered to be activating immunotherapies and there are no additional time restrictions on prior exposure to these agents (except prior brentuximab vedotin)
Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) performance status between 0-2
Patients must have measurable disease; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by a diagnostic quality CT scan; patients must use the same imaging modality (CT or PET/CT) throughout the study
Patient must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a patient of childbearing potential is anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Patient of childbearing potential and/or sexually active patients must either abstain from sexual intercourse for the duration of their participation in the study or agree to use both single barrier contraception and birth control pills or implants for at least one week prior to the start of the study drug and continuing for 5 months after the last dose of study drug (for patients of childbearing potential) and for 7 months after the last dose of study drug (for patients who are sexually active with anyone of childbearing potential); should a patient become pregnant or suspect pregnancy while the patient or their partner is participating in this study, the patient (or the participating partner) should inform the treating physician immediately
Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92% while breathing room air
Patients must have forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
Absolute neutrophil count (ANC) >= 1500/mcL (1.5 x 10\^9/L) (obtained within 2 weeks prior to registration)
Platelets >= 75,000/mcL (75 x 10\^9/L) (obtained within 2 weeks prior to registration)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN) (obtained within 2 weeks prior to registration)
Bilirubin =\< 2 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =\< 3 x upper limit of normal [ULN] is permitted) (obtained within 2 weeks prior to registration)
Calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy continuously disease free for >= 5 years so as not to interfere with interpretation of radiographic response
Patient must have no current or prior history of central nervous system (CNS) involvement
All prior therapy must have been completed at least 21 days prior to enrollment; no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
No history of Steven's Johnson's syndrome, toxic epidermal necrolysis (TEN)s syndrome, or motor neuropathy
Human immunodeficiency virus (HIV) positive patients are allowed on this study if they have a CD4 count > 400, and are on a stable antiviral regimen; patients with poorly controlled HIV or other chronic active viral infections will be excluded
Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed
- Replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of these classes of medication for at least 2 weeks prior to initiation of study treatment are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study
- Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia Gravis); other CNS autoimmune disease (e.g., Multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
Patients must not have grade 2 or greater peripheral sensory neuropathy
Patients must not have New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
Patients must not have previously existing hypersensitivity to brentuximab vedotin or ipilimumab
Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
Patients must not be participating in any other clinical trial or taking any other experimental medications within 21 days prior to registration
Routine vaccinations, including seasonal influenza, should be given at least 2 weeks prior to study treatment; vaccines are not prohibited on study, but must be given at least 6 weeks after cycle 1 and not within 7 days of treatment
Patients registering to Arms D, E, F, G, H, I, X, Y must not currently be smoking tobacco or other substances and must not have smoked within the past 6 months
RANDOMIZED PHASE II (ARMS K AND L): Age >= 12 years
- Pediatric patients will include any patients \< 18 years of age
RANDOMIZED PHASE II (ARMS K AND L): Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
RANDOMIZED PHASE II (ARMS K AND L): Patients must have relapsed after first line chemotherapy; may have relapsed after autologous stem cell transplant, or have primary refractory disease; no upper limit for number of prior therapies; patient must not have received a prior allogeneic stem cell transplant (out of risk of reactivation of pulmonary graft versus host disease [GVHD])
RANDOMIZED PHASE II (ARMS K AND L): Patients may have received prior brentuximab vedotin, but must not have received brentuximab vedotin within 6 months prior to registration, and must not have relapsed within 6 months of receiving previous brentuximab vedotin; patients may not have received prior nivolumab or PD1/PDL1 axis agents; patients may not have received prior ipilimumab
RANDOMIZED PHASE II (ARMS K AND L): Patients may not have received other prior activating immunotherapies (i.e. checkpoint inhibitor therapies); for the purposes of this study monoclonal antibodies and antibody drug conjugates are not considered to be activating immunotherapies and there are no additional time restrictions on prior exposure to these agents (except prior brentuximab vedotin)
RANDOMIZED PHASE II (ARMS K AND L): Adult patient (>= 18 years of age) ECOG-ACRIN performance status between 0-2
- Pediatric patients (16-17 years of age) must have a Karnofsky performance level >= 50%
- Pediatric patients (12-15 years of age) must have a Lansky performance level >= 50
RANDOMIZED PHASE II (ARMS K AND L): Patients must have measurable disease; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by a diagnostic quality CT scan; patients must use the same imaging modality (CT or PET/CT) throughout the study
RANDOMIZED PHASE II (ARMS K AND L): Patient must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
RANDOMIZED PHASE II (ARMS K AND L): Patient of childbearing potential and/or sexually active patient must either abstain from sexual intercourse for the duration of their participation in the study or agree to use both double barrier contraception and birth control pills or implants for at least one week prior to the start of the study drug and continuing for 5 months after the last dose of study drug (for patients of childbearing potential) and for 7 months after the last dose of study drug (for patients who are sexually active with anyone of childbearing potential); should a patient become pregnant or suspect pregnancy while the patient or their partner is participating in this study, the patient (or the participating partner) should inform the treating physician immediately
RANDOMIZED PHASE II (ARMS K AND L): Patients with impaired decision-making capacity are eligible with legally authorized representative
RANDOMIZED PHASE II (ARMS K AND L): Patients must have no evidence of dyspnea at rest and a pulse oximetry > 92% while breathing room air
RANDOMIZED PHASE II (ARMS K AND L): Patients must have FEV1/FVC > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
RANDOMIZED PHASE II (ARMS K AND L): ANC >= 1500/mcL (1.5 x 0\^9/L) (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): Platelets >= 75,000/mcL (75 x 10\^9/L) (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): AST/ALT =\< 2.5 x upper limit of normal (ULN) for age (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): Bilirubin =\< 2 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =\< 3 x upper limit of normal [ULN] is permitted) (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): Adult patients (>= 18 years old) must have a calculated creatinine clearance by Cockcroft-Gault formula >= 30 ml/min (obtained within 2 weeks prior to registration)
RANDOMIZED PHASE II (ARMS K AND L): Pediatric patients (\< 18 years old) must have a creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m\^2 or serum creatinine based on age/sex as follows:
- Age: maximum serum creatinine (mg/dL)
  - \< 13 years: male (1.2), female (1.2)
  - 13 to \< 16 years: male (1.5), female (1.4)
  - >= 16 years: male (1.7), female (1.4)
RANDOMIZED PHASE II (ARMS K AND L): No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma or any surgically- or radiation-cured malignancy continuously disease free for >= 5 years so as not to interfere with interpretation of radiographic response
RANDOMIZED PHASE II (ARMS K AND L): Patient must have no current or prior history of CNS involvement
RANDOMIZED PHASE II (ARMS K AND L): All prior therapy must have been completed at least 21 days prior to enrollment (6 weeks for nitrosoureas or mitomycin C); no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
RANDOMIZED PHASE II (ARMS K AND L): No history of Steven's Johnson's syndrome, TENs syndrome, or motor neuropathy
RANDOMIZED PHASE II (ARMS K AND L): HIV positive patients are eligible provided they meet the other protocol criteria including the following:
- Long term survival expected were it not for the cHL
- HIV viral loads undetectable by standard clinical HIV testing
- Willing to adhere to effective combination antiretroviral therapy
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have autoimmune disorders, prior solid organ transplant, or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed; replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of steroid medication for at least 2 weeks prior to initiation of therapy are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study; exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia Gravis); other CNS autoimmune disease (e.g., Multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have grade 2 or greater peripheral sensory neuropathy
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have NYHA class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have previously existing hypersensitivity to brentuximab vedotin or ipilimumab
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
RANDOMIZED PHASE II (ARMS K AND L): Patients must not be participating in any other clinical trial or taking any other experimental medications within 21 days prior to registration
RANDOMIZED PHASE II (ARMS K AND L): Routine vaccinations, including seasonal influenza, should be given at least 2 weeks prior to study treatment; vaccines are not prohibited on study, but must be given at least 6 weeks after cycle 1 and not within 7 days of treatment
RANDOMIZED PHASE II (ARMS K AND L): Patients must not currently be smoking tobacco or other agents; vaping is not allowed
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a history of or evidence of cardiovascular risks including any of the following:
- QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec at baseline
- History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to registration
- History prior to registration or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system
- Left ventricular ejection fraction (LVEF) =\< lower limit of normal on cardiac echocardiogram (echo) or multigated acquisition scan (MUGA)
- Intra-cardiac defibrillator
- History of abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
- History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible
- Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 146 participants (estimated)

Study arms

Experimental
Phase I Arm I (brentuximab vedotin, ipilimumab)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 of cycles 1-16 and ipilimumab IV over 90 minutes on day 1 of cycles 1-4, 8, 12, and 16. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Brentuximab Vedotin · Procedure: Computed Tomography · Biological: Ipilimumab · Procedure: Positron Emission Tomography
Experimental
Phase I Arm II (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-46. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Brentuximab Vedotin · Procedure: Computed Tomography · Biological: Nivolumab · Procedure: Positron Emission Tomography
Experimental
Phase I Arm III (brentuximab vedotin, nivolumab, ipilimumab)
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-46, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 16 cycles and every 14 days beginning cycle 17 for up to 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Brentuximab Vedotin · Procedure: Computed Tomography · Biological: Ipilimumab · Biological: Nivolumab · Procedure: Positron Emission Tomography
Experimental
Phase II Arm I (brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16 and nivolumab IV over 30 minutes on day 1 of cycles 1-34. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Brentuximab Vedotin · Procedure: Computed Tomography · Biological: Nivolumab · Procedure: Positron Emission Tomography
Experimental
Phase II Arm II (brentuximab vedotin, nivolumab, ipilimumab)
Patients receive brentuximab vedotin IV over 90 minutes on day 1 of cycles 1-16, nivolumab IV over 30 minutes on day 1 of cycles 1-34, and ipilimumab IV over 30 minutes on day 1 every 12 weeks for up to 9 doses. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET scan throughout the trial. Patients undergo blood sample collection and may undergo tumor biopsy on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Brentuximab Vedotin · Procedure: Computed Tomography · Biological: Ipilimumab · Biological: Nivolumab · Procedure: Positron Emission Tomography

Interventions

ProcedureBiopsy Procedure
Undergo biopsy
Also known as: Biopsy, BIOPSY_TYPE, Bx
ProcedureBiospecimen Collection
Undergo collection of blood
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
DrugBrentuximab Vedotin
Given IV
Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN 35, SGN-35, SGN35
ProcedureComputed Tomography
Undergo CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography
BiologicalIpilimumab
Given IV
Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016, Ipilimumab Biosimilar CS1002, MDX 010, MDX-010, MDX-CTLA4, MDX010, Yervoy
BiologicalNivolumab
Given IV
Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo
ProcedurePositron Emission Tomography
Undergo PET
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

What researchers measure

Primary outcomes

Maximum tolerated dose (MTD) of each combination (Phase I)
MTD defined as the highest dose level at which less than 33% of 6 patients experience a dose limiting toxicity, will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Upon completion of the trial, frequency of subjects experiencing toxicities will be tabulated. Toxicities will be assessed and graded according to CTCAE version 4.0 terminology. Exact 95% confidence intervals (CI) around the toxicity proportions will be calculated.
Time frame: 21 days
CR rate (Phase II)
The analysis of CR between two arms will be performed using exact Cochran-Mantel-Haenszel (CMH) test stratifying on prior brentuximab vedotin (BV) (yes versus \[vs.\] no) and age (\< 18 vs. \>= 18). Multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
Time frame: Up to 10 years

Secondary outcomes

Complete response (CR) rate (Phase I)
Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI.
Time frame: Up to 3 years
Partial response (PR) rate (Phase I)
Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI.
Time frame: Up to 3 years
Overall response rate (ORR) rate (Phase I)
Assessed using the Revised Response Criteria for Malignant Lymphoma and reported along with the 95% CI.
Time frame: Up to 3 years
Duration of response (DOR) (Phase I)
DOR will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates. Descriptive statistics will be used to evaluate the DOR achieved with the protocol therapy and with the most recent prior systemic therapy.
Time frame: From the documented beginning of response up to 3 years
Overall survival (OS) (Phase I)
OS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates.
Time frame: From the date of study entry up to 3 years
Progression-free survival (PFS) (Phase I)
PFS will be estimated using Kaplan-Meier methodology. Greenwood's formula will be used to calculate 95% CI for the Kaplan-Meier estimates.
Time frame: From entry onto study up to 3 years
ORR (Phase II)
Assessed using Revised Response (Cheson) and Deauville criteria. The analysis of ORR between two arms will be performed using the CMH test stratifying on prior BV (yes vs. no) and age (\< 18 vs. \>= 18). Multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
Time frame: Up to 10 years
PFS (or modified PFS) (Phase II)
PFS will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome. Point estimates of all endpoints will be accompanied by the corresponding 95% confidence intervals.
Time frame: From randomization up to 10 years
OS (Phase II)
OS will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome. Point estimates of all endpoints will be accompanied by the corresponding 95% confidence intervals.
Time frame: From randomization up to 10 years
DOR (Phase II)
DOR, will be estimated using Kaplan-Meier methodology and compared between arms using stratified log-rank test. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier estimates. Cox proportional regression model will be used to estimate hazard ratios (95% CI) and assess the relationship between other prognostic factors with time-to-event outcome. Point estimates of all endpoints will be accompanied by the corresponding 90% confidence intervals. The DOR achieved with the most recent prior systemic therapy will be collected on the case report forms, and descriptive statistics will be used to evaluate the DOR achieved with the protocol therapy and with the most recent prior systemic therapy.
Time frame: From the documented beginning of response up to 10 years

Other outcomes

Change in the percentage of activated T cells and natural killer cells (Phase I and II)
These quantities of interest will be calculated for each patient and the Wilcoxon signed-rank test will be used to test for significant difference between the time points. Using Wilcoxon rank sum test (two-sided type I error of 0.1), differences between those who progress or die within one year versus (vs.) those who are event-free at one year will be evaluated.
Time frame: Baseline (Time 1) to 9 weeks (Time 3, time of first re-staging)
Change in the percentages of activated T cells and natural killer cells (Phase I and II)
These quantities of interest will be calculated for each patient and the Wilcoxon signed-rank test will be used to test for significant difference between the time points. Using the Wilcoxon rank sum test (two-sided type I error of 0.1), differences between those who progress or die within one year vs. those who are event-free at one year will be evaluated.
Time frame: Day 1 of cycle 2 (Time 2) or 9 weeks (Time 3) to up to 6 weeks after completion of study treatment (Time 4, end of study)
Effects of combinations on systemic immunity (Phase I and II)
Time frame: Baseline to up to 6 weeks after completion of study treatment
Pre- and post-treatment levels of cytokines and T cell specific biomarkers (Phase I and II)
Pre- and post-treatment levels of these markers will be compared using the Wilcoxon signed-rank test with two-sided type I error of 0.1. Marker levels between patients who fail at 1-year vs. patients who are event-free at 1-year will be evaluated. Given limited data, the analyses of PD-1, co-expression of Tim-3 with PD-1, ICOS, sCD30, galectin-1 and the peripheral blood absolute lymphocyte to monocyte ratio will be mainly exploratory and will be summarized descriptively at the time-points described above. The association with PFS will be explored.
Time frame: Baseline to up to 6 weeks after completion of study treatment
Differentially expressed genes between two groups (patients who fail at 1-year vs. patients who are event-free at 1-year or responders vs. non-responders) (Phase I and II)
Assessed using gene expression profiling (GEP). Differentially expressed genes will be identified using a rank-based method developed by Dr. Hong (RankProd, R package, Bioconductor Project) with multiple comparison adjustment using a false discovery rate approach. A two-way unsupervised hierarchical clustering analysis will be applied to both the genes and the samples to illustrate whether GEP can separate two groups or is associated with other clinical factors. The genes ranked as most significant will be assessed by gene ontology and pathway analysis for their potential functions in lymphoma biology and treatment failure.
Time frame: 1 year
Microbiome analysis (Phase I and II)
Will compare the gut microbiome between Hodgkin lymphoma (HL) patients and healthy controls with respect to global diversity, taxonomic abundance, and bacterial functional pathways. The relative abundance of each taxon (phyla to genera) and functional pathways among different groups will be statistically compared in univariate analysis using t-test (or Wilcoxon test) and in multivariate analysis using logistic regression. Global diversity tests and multivariate analysis for taxonomic abundance and functional pathways will be adjusted for potential confounders (age, sex, race, and body mass index) in the comparisons of HL patients and controls, and further adjusted for stage and grade when examining the clinical response among HL patients.
Time frame: Completion of study treatment
Absolute maximum standard uptake value (SUVmax) (Phase II)
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, event free survival (EFS), OS 5PS in two reading settings (1-3 \[negative\] vs 4-5 \[positive\] and D 5PS 1-4 \[negative\] vs 5 \[positive\]) (Kaplan-Meier \[KM\] curve and log-rank testing).
Time frame: Up to cycle 10
Metabolic whole body tumor volume (MTV) and tumor lesion glycolysis (TLG)
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 \[negative\] vs 4-5 \[positive\] and D 5PS 1-4 \[negative\] vs 5 \[positive\]) (KM curve and log-rank testing).
Time frame: Up to cycle 10
Percent change in SUVmax, MTV and TLG between baseline and during therapy
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 \[negative\] vs 4-5 \[positive\] and D 5PS 1-4 \[negative\] vs 5 \[positive\]) (KM curve and log-rank testing).
Time frame: Baseline up to cycle 10
Percent change in size (sum of perpendicular diameters [SPD]) on computed tomography (CT)
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 \[negative\] vs 4-5 \[positive\] and D 5PS 1-4 \[negative\] vs 5 \[positive\]) (KM curve and log-rank testing).
Time frame: Baseline up to cycle 10
Absolute CT tumor volumes
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 \[negative\] vs 4-5 \[positive\] and D 5PS 1-4 \[negative\] vs 5 \[positive\]) (KM curve and log-rank testing).
Time frame: Up to cycle 10
Percent change in CT size (SPD) and in CT tumor volume between baseline and during therapy
Image data will be evaluated using Lugano response criteria with various D 5PS cut-offs in the entire cohort and in different therapy cohorts to determine if the existing set of criteria is sufficient to segregate the group into various response categories. Will correlate PFS, EFS, OS 5PS in two reading settings (1-3 \[negative\] vs 4-5 \[positive\] and D 5PS 1-4 \[negative\] vs 5 \[positive\]) (KM curve and log-rank testing).
Time frame: Baseline up to cycle 10

Study locations

479 sites

Children's Hospital of Alabama
Birmingham, Alabama 35233, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233, United States
Anchorage Associates in Radiation Medicine
Anchorage, Alaska 98508, United States
Anchorage Radiation Therapy Center
Anchorage, Alaska 99504, United States
Alaska Breast Care and Surgery LLC
Anchorage, Alaska 99508, United States
Alaska Oncology and Hematology LLC
Anchorage, Alaska 99508, United States
Alaska Women's Cancer Care
Anchorage, Alaska 99508, United States
Anchorage Oncology Centre
Anchorage, Alaska 99508, United States
Katmai Oncology Group
Anchorage, Alaska 99508, United States
Providence Alaska Medical Center
Anchorage, Alaska 99508, United States
Fairbanks Memorial Hospital
Fairbanks, Alaska 99701, United States
Kingman Regional Medical Center
Kingman, Arizona 86401, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona 85004, United States
Mercy Hospital Fort Smith
Fort Smith, Arkansas 72903, United States
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs, Arkansas 71913, United States
Kaiser Permanente-Deer Valley Medical Center
Antioch, California 94531, United States
Mission Hope Medical Oncology - Arroyo Grande
Arroyo Grande, California 93420, United States
PCR Oncology
Arroyo Grande, California 93420, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California 91505, United States
Kaiser Permanente Dublin
Dublin, California 94568, United States
Kaiser Permanente-Fremont
Fremont, California 94538, United States
Fresno Cancer Center
Fresno, California 93720, United States
Kaiser Permanente-Fresno
Fresno, California 93720, United States
Kaiser Permanente-Modesto
Modesto, California 95356, United States
Kaiser Permanente Oakland-Broadway
Oakland, California 94611, United States
Kaiser Permanente-Oakland
Oakland, California 94611, United States
Children's Hospital of Orange County
Orange, California 92868, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California 94304, United States
Kaiser Permanente-Rancho Cordova Cancer Center
Rancho Cordova, California 95670, United States
Kaiser Permanente-Redwood City
Redwood City, California 94063, United States
Kaiser Permanente-Richmond
Richmond, California 94801, United States
Rohnert Park Cancer Center
Rohnert Park, California 94928, United States
Kaiser Permanente-Roseville
Roseville, California 95661, United States
The Permanente Medical Group-Roseville Radiation Oncology
Roseville, California 95678, United States
Kaiser Permanente Downtown Commons
Sacramento, California 95814, United States
Kaiser Permanente-South Sacramento
Sacramento, California 95823, United States
South Sacramento Cancer Center
Sacramento, California 95823, United States
Kaiser Permanente Sacramento Medical Center
Sacramento, California 95825, United States
Kaiser Permanente-San Francisco
San Francisco, California 94115, United States
UCSF Medical Center-Mission Bay
San Francisco, California 94158, United States
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California 95119, United States
Kaiser Permanente San Leandro
San Leandro, California 94577, United States
Pacific Central Coast Health Center-San Luis Obispo
San Luis Obispo, California 93401, United States
Kaiser Permanente-San Rafael
San Rafael, California 94903, United States
Kaiser San Rafael-Gallinas
San Rafael, California 94903, United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California 95051, United States
Mission Hope Medical Oncology - Santa Maria
Santa Maria, California 93444, United States
Kaiser Permanente-Santa Rosa
Santa Rosa, California 95403, United States
Kaiser Permanente Cancer Treatment Center
South San Francisco, California 94080, United States
Kaiser Permanente-South San Francisco
South San Francisco, California 94080, United States
Kaiser Permanente-Stockton
Stockton, California 95210, United States
Kaiser Permanente Medical Center-Vacaville
Vacaville, California 95688, United States
Kaiser Permanente-Vallejo
Vallejo, California 94589, United States
Kaiser Permanente-Walnut Creek
Walnut Creek, California 94596, United States
Rocky Mountain Cancer Centers-Aurora
Aurora, Colorado 80012, United States
The Medical Center of Aurora
Aurora, Colorado 80012, United States
Boulder Community Foothills Hospital
Boulder, Colorado 80303, United States
Rocky Mountain Cancer Centers-Boulder
Boulder, Colorado 80304, United States
Rocky Mountain Cancer Centers - Centennial
Centennial, Colorado 80112, United States
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado 80907, United States
Rocky Mountain Cancer Centers-Penrose
Colorado Springs, Colorado 80907, United States
Cancer Center of Colorado at Sloan's Lake
Denver, Colorado 80204, United States
Denver Health Medical Center
Denver, Colorado 80204, United States
National Jewish Health-Main Campus
Denver, Colorado 80206, United States
The Women's Imaging Center
Denver, Colorado 80209, United States
AdventHealth Porter
Denver, Colorado 80210, United States
Colorado Blood Cancer Institute
Denver, Colorado 80218, United States
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado 80218, United States
Rocky Mountain Cancer Centers-Midtown
Denver, Colorado 80218, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado 80218, United States
Saint Joseph Hospital - Cancer Centers of Colorado
Denver, Colorado 80218, United States
Rocky Mountain Cancer Centers-Rose
Denver, Colorado 80220, United States
Rose Medical Center
Denver, Colorado 80220, United States
Western Surgical Care
Denver, Colorado 80220, United States
CommonSpirit Cancer Center Mercy
Durango, Colorado 81301, United States
Mercy Medical Center
Durango, Colorado 81301, United States
Mountain Blue Cancer Care Center - Swedish
Englewood, Colorado 80113, United States
Rocky Mountain Cancer Centers - Swedish
Englewood, Colorado 80113, United States
Swedish Medical Center
Englewood, Colorado 80113, United States
Mountain Blue Cancer Care Center
Golden, Colorado 80401, United States
National Jewish Health-Western Hematology Oncology
Golden, Colorado 80401, United States
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado 81501, United States
Banner North Colorado Medical Center
Greeley, Colorado 80631, United States
Good Samaritan Hospital - Cancer Centers of Colorado
Lafayette, Colorado 80026, United States
CommonSpirit Saint Anthony Hospital Cancer Center
Lakewood, Colorado 80228, United States
Rocky Mountain Cancer Centers-Lakewood
Lakewood, Colorado 80228, United States
Rocky Mountain Cancer Centers-Littleton
Littleton, Colorado 80120, United States
AdventHealth Littleton
Littleton, Colorado 80122, United States
Rocky Mountain Cancer Centers-Sky Ridge
Lone Tree, Colorado 80124, United States
Sky Ridge Medical Center
Lone Tree, Colorado 80124, United States
Longmont United Hospital
Longmont, Colorado 80501, United States
Rocky Mountain Cancer Centers-Longmont
Longmont, Colorado 80501, United States
Banner North Colorado Medical Center - Loveland Campus
Loveland, Colorado 80539, United States
AdventHealth Parker
Parker, Colorado 80138, United States
Rocky Mountain Cancer Centers-Parker
Parker, Colorado 80138, United States
Rocky Mountain Cancer Centers - Pueblo
Pueblo, Colorado 81008, United States
National Jewish Health-Northern Hematology Oncology
Thornton, Colorado 80260, United States
Rocky Mountain Cancer Centers-Thornton
Thornton, Colorado 80260, United States
Intermountain Health Lutheran Hospital
Wheat Ridge, Colorado 80401, United States
Children's National Medical Center
Washington D.C., District of Columbia 20010, United States

Showing the first 100 of 479 sites.

References and documents

Publications

Diefenbach CS, Jegede O, Wang V, Ansell SM, Kostakoglu L, Steidl C, Natkunam Y, Scott DW, Ambinder RF, David KA, Advani RH, Bartlett NL, Robertson MJ, Thomas SP, Cohen J, Ibrahimi S, Goyal G, Mehta-Shah N, Amengual JE, Forlenza CJ, Cole PD, Duan F, Kelly K, Kahl BS. A randomized phase 2 study of ipilimumab, nivolumab, and brentuximab vedotin in patients with relapsed Hodgkin lymphoma. Blood. 2026 Apr 30;147(18):2041-2052. doi: 10.1182/blood.2025029546. PubMed 41662628 ↗
Gonzalez-Kozlova E, Huang HH, Jagede OA, Tuballes K, Del Valle DM, Kelly G, Patel M, Xie H, Harris J, Argueta K, Nie K, Barcessat V, Moravec R, Altreuter J, Duose DY, Kahl BS, Ansell SM, Yu J, Cerami E, Lindsay JR, Wistuba II, Kim-Schulze S, Diefenbach CS, Gnjatic S. Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma. Cancer Res Commun. 2024 Jul 1;4(7):1726-1737. doi: 10.1158/2767-9764.CRC-24-0252. PubMed 38934093 ↗
Mu-Mosley H, von Itzstein MS, Fattah F, Liu J, Zhu C, Xie Y, Wakeland EK, Park JY, Kahl BS, Diefenbach CS, Gerber DE. Distinct autoantibody profiles across checkpoint inhibitor types and toxicities. Oncoimmunology. 2024 May 9;13(1):2351255. doi: 10.1080/2162402X.2024.2351255. eCollection 2024. PubMed 38737792 ↗
Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28. PubMed 37505794 ↗
Diefenbach CS, Hong F, Ambinder RF, Cohen JB, Robertson MJ, David KA, Advani RH, Fenske TS, Barta SK, Palmisiano ND, Svoboda J, Morgan DS, Karmali R, Sharon E, Streicher H, Kahl BS, Ansell SM. Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2020 Sep;7(9):e660-e670. doi: 10.1016/S2352-3026(20)30221-0. PubMed 32853585 ↗

Updates

1 registry update since Sep 25, 2026

Primary completion

Dec 31, 2026→Jun 30, 2027

Sep 29, 2026

Study completion

Dec 31, 2026→Jun 30, 2027

Sep 29, 2026

Show all 1 update

Sep 29, 2026
Primary completion Dec 31, 2026→Jun 30, 2027
Study completion Dec 31, 2026→Jun 30, 2027
+ 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01896999
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Jul 11, 2013
Start date: Mar 7, 2014
Primary completion: Jun 30, 2027 (estimated)
Completion: Jun 30, 2027 (estimated)
Last update: Sep 29, 2026

Study contacts

Catherine S Diefenbach

principal investigator · ECOG-ACRIN Cancer Research Group

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

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