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CompletedNCT03586999Updated Oct 29, 2024Results posted

Nivolumab With Standard of Care Chemotherapy for Peripheral T Cell Lymphomas

A Phase 1/2 interventional study of Nivolumab and Etoposide in Peripheral T Cell Lymphoma, sponsored by University of Colorado, Denver. Completed at 3 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-10-29.

Sponsored by University of Colorado, Denver · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
18
Allocation
Not applicable
Ages
18 Years to 80 Years
Sex
All
01

Study summary

This regimen aims to become the first line treatment for peripheral T cell lymphoma, using nivolumab with the standard of care chemotherapy.

Read the detailed description

Patients in this study will receive nivolumab in combination with the standard of care dose-adjusted EPOCH (etoposide, prednisone, vincristine, doxorubicin, cyclophosphamide) for six 21 day cycles. Patients will then have an autologous stem cell transplant or continue to receive maintenance therapy with nivolumab.

02

Conditions studied

  • Peripheral T Cell Lymphoma

Keywords

  • Nivolumab
  • First Line Treatment
  • EPOCH
  • Standard of Care
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 18 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

University of Colorado, Denver is the lead sponsor of 1,499 studies on the registry; 315 are open to participants now.

Of its 139 completed or terminated interventional studies of FDA-regulated products, 89 (64%) have results posted.

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

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

  1. Ability to sign and date the consent form.
  2. Stated willingness to comply with all study procedures and be available for the duration of the study.
  3. Be a male or female aged 18-80.
  4. Histologically confirmed new diagnosis of Stage II, III or IV Peripheral T-cell Non-Hodgkin's lymphoma not otherwise specified (NOS), Anaplastic large cell lymphoma (ALK-negative) (ALK-positive if IPI 3, 4, or 5), Angioimmunoblastic T-cell lymphoma, Enteropathy associated T-cell lymphoma (MEITL and EATL), Hepatosplenic T-cell lymphoma, y/8 T-cell lymphoma, Subcutaneous panniculitis-like T-cell lymphoma, and Nodal T-cell lymphomas with T-follicular helper phenotype.
  5. Available pathology material (fine needle aspirate is inadequate) for review at the University of Colorado.
  6. No prior therapy with the exception of prior radiation therapy and/or 1 cycle of chemotherapy (may be any chemotherapy regimen or even prednisone alone) based on current diagnosis and clinical condition. If given cytotoxic chemotherapy (one cycle only, e.g. CHOP), this cycle of treatment will count toward the 6 cycles of treatment given in the study.
  7. ECOG performance status 0 - 2.

  8. Laboratory status as follows:

    • ANC > 1000 cells/mm3, unless cytopenias due to lymphoma (i.e., bone marrow involvement or splenomegaly)
    • Platelet Count > 100,000 /μL, or > 50,000 /μL if bone marrow involvement or splenomegaly
    • Total bilirubin ≤1.5 x upper normal limit, or ≤ 3 x upper normal limit if documented hepatic involvement with lymphoma, or ≤ 5 x upper normal limit if history of Gilbert's Disease.
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper normal limit (≤ 5 x upper normal limit if documented hepatic involvement with lymphoma).
    • Serum creatinine \< 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45 mL/min (Cockcroft-Gault, Appendix)
    • PT or INR, and PTT ≤ 1.5 x upper limit of normal unless patient is receiving anticoagulants. If patient is on warfarin therapy, levels should be within therapeutic range.
  9. Patients with measurable disease. Measurable disease is defined as having at least one objective measurable disease parameter. A clearly defined, bi-dimensionally measurable defect or mass measuring at least 1.5 cm in diameter on the CT portion of a PET/CT or CT scan or MRI (if appropriate) will constitute measurable disease. Proof of lymphoma in the liver is required by a confirmation biopsy unless there is measurable disease by imaging. Skin lesions can be used as measurable disease provided bi-dimensional measurements are possible. Patients with non-measurable but evaluable disease may be eligible after discussion with the PI. Abnormal PET/CT scans will not constitute evaluable disease, unless verified by the CT scan portion, CT scan, or other appropriate imaging.
  10. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use of contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 180 days after the last study treatment. A woman is considered to be of childbearing potential if she is post-menarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  11. Patient must be able to adhere to the study visit schedule and other protocol requirements.

Exclusion criteria

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

  1. An additional malignancy treated with palliative intent within the past 2 years. Malignancies in patients who have completed definitive treatment with curative intent >1 year will be permitted after discussion with the PI. Adequately treated basal cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or breast; prostate cancer of Gleason Grade 6 or less with stable PSA levels are allowed.
  2. Patients with a diagnosis of other PTCL histologies other than those specified in the inclusion criteria.
  3. Primary T-cell CNS lymphoma; however, secondary CNS disease is not an exclusion criteria.
  4. Pregnant or breastfeeding females.
  5. Contraindication to any of the required concomitant drugs or supportive treatments.
  6. Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
  7. Ejection fraction of \<45% by either MUGA or ECHO.
  8. Has immunodeficiency or is being treated with immuno-suppressive therapy (aside from medications used to treat lymphoma) within 7 days of first dose of study treatment. Inhaled or topical steroids are accepted. Prednisone used to treat adrenal insufficiency in the absence of auto-immune disease is also acceptable.
  9. Auto-immune condition requiring immuno-suppressive disease modifying therapy within the prior 2 years. Replacement therapy, e.g. levothyroxine for thyroiditis or insulin for diabetes are acceptable.
  10. History of non-infectious pneumonitis requiring immuno-suppressive therapy.
  11. Active hepatitis B or C (with measurable virus or antigen in serum) or HIV. Patients who are seropositive because of hepatitis B virus vaccine or have a history of hepatitis B (with no measurable virus or antigen in serum) are eligible.
  12. Prior PD-1 or PD-L1 antibody treatment.
  13. Has received a live virus vaccine in 30 days preceding start of therapy.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
18 participants (actual)

Study arms

  • Experimental
    Nivolumab and EPOCH

    Patients will all receive nivolumab in combination with standard dose adjusted EPOCH for a planned 6 cycles, unless treatment is stopped early for disease progression or toxicity. Patients that have already received up to 1 cycle of standard of care chemotherapy will receive 5 cycles of experimental nivolumab + DA-EPOCH (dose adjusted, continuous infusion etoposide, prednisone, vincristine, doxorubicin, and bolus dosing of cyclophosphamide) for a total of 6 cycles of chemotherapy.

    Drug: Nivolumab · Drug: Etoposide · Drug: Prednisolone · Drug: Oncovin · Drug: Cyclophosphamide · Drug: Hydroxydaunorubicin

Interventions

  • DrugNivolumab

    Nivolumab injection is to be administered as an IV infusion.

    Also known as: Opdivo

  • DrugEtoposide

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the Mosteller formula and administered through IV. Dose adjustments at the beginning of each cycle do not need to be made unless there has been a \>10% weight gain or loss. Patients receive six 21-day cycles of the medications.

    Also known as: Vepesid, Toposar

  • DrugPrednisolone

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the Mosteller formula and administered through IV. Dose adjustments at the beginning of each cycle do not need to be made unless there has been a \>10% weight gain or loss. Patients receive six 21-day cycles of the medications.

    Also known as: Oraped, PediaPred, Millipred

  • DrugOncovin

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the Mosteller formula and administered through IV. Dose adjustments at the beginning of each cycle do not need to be made unless there has been a \>10% weight gain or loss. Patients receive six 21-day cycles of the medications.

    Also known as: Vincristine, Leurocristine

  • DrugCyclophosphamide

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the Mosteller formula and administered through IV. Dose adjustments at the beginning of each cycle do not need to be made unless there has been a \>10% weight gain or loss. Patients receive six 21-day cycles of the medications.

    Also known as: cytophosphane

  • DrugHydroxydaunorubicin

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the Mosteller formula and administered through IV. Dose adjustments at the beginning of each cycle do not need to be made unless there has been a \>10% weight gain or loss. Patients receive six 21-day cycles of the medications.

    Also known as: Adriamycin

06

What researchers measure

Primary outcomes

  1. Efficacy: Complete Response Rate

    Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.

    Time frame: up to 100 days post transplant

Secondary outcomes

  1. Number of Participants With Adverse Events

    Toxicity analysis of nivolumab will be summarized by dose and severity as assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 and relationship to study drug or the amount of grade 4-5 non-hematologic toxicities.

    Time frame: up to 100 days after last dose of nivolumab

  2. Efficacy: Overall Response Rate

    Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy. Complete response (CR), complete disappearance of all target lesions and Deauville score 1-3. Partial response (PR), ≥30% decrease in the sum of longest diameters of target lesions but not a CR and Deauville score 4-5. Stable disease (SD), \<30% decrease or ≤ 20% increase in the sum of longest diameters of target lesions. Progressive disease (PD), \>20% increase in the sum of longest diameters of target lesions, For small lymph nodes measuring \< 15 mm post-therapy, a minimum of 5 mm increase in longest diameter to \> 15 mm, or new lesions.

    Time frame: up to 100 days post transplant

  3. Efficacy: Progression Free Survival Rate

    Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.

    Time frame: up to 2 years after completion of treatment

  4. Efficacy: Event Free Survival

    Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy. Events defined as start of new treatment, progression, or death.

    Time frame: up to 2 years after completion of treatment

  5. Immune-related Predictors of Response

    We assessed PD-L1 expression using immunohistochemistry on pre-treatment tumor tissue. The outcome of measurement was complete response yes vs. no. Using logistic regression, we assessed if the percentage of PDL1+ cells was predictive of achieving a complete response.

    Time frame: Within 6 months of treatment

07

Results

Posted Oct 29, 2024

Participant flow

Participant flow — Overall Study
MilestoneNivolumab and EPOCH
Started18
Completed16
Not completed2
Withdrew: Lack of efficacy2

Outcome measures

PrimaryEfficacy: Complete Response Rate

Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.

Time frame:
up to 100 days post transplant
Reported as:
Count of participants · Participants
Efficacy: Complete Response Rate
ParticipantsNivolumab and EPOCH
Efficacy: Complete Response Rate11
Statistical analysis
  • Nivolumab and EPOCH · t-test, 2 sided · p = .1 (The proportion achieving a complete response will be calculated and will compared to null proportion of 30%. The population proportion for complete response rate, p-value and 90% confidence intervals for the complete response rate will be calculated.) · Proportion: 0.3
SecondaryNumber of Participants With Adverse Events

Toxicity analysis of nivolumab will be summarized by dose and severity as assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 and relationship to study drug or the amount of grade 4-5 non-hematologic toxicities.

Time frame:
up to 100 days after last dose of nivolumab
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events
ParticipantsNivolumab and EPOCH
Number of Participants With Adverse Events18
SecondaryEfficacy: Overall Response Rate

Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy. Complete response (CR), complete disappearance of all target lesions and Deauville score 1-3. Partial response (PR), ≥30% decrease in the sum of longest diameters of target lesions but not a CR and Deauville score 4-5. Stable disease (SD), \<30% decrease or ≤ 20% increase in the sum of longest diameters of target lesions. Progressive disease (PD), \>20% increase in the sum of longest diameters of target lesions, For small lymph nodes measuring \< 15 mm post-therapy, a minimum of 5 mm increase in longest diameter to \> 15 mm, or new lesions.

Time frame:
up to 100 days post transplant
Reported as:
Count of participants · Participants
Efficacy: Overall Response Rate
ParticipantsNivo and EPOCH
Efficacy: Overall Response Rate16
SecondaryEfficacy: Progression Free Survival Rate

Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.

Time frame:
up to 2 years after completion of treatment
Reported as:
Median · months
Efficacy: Progression Free Survival Rate
monthsNivo and EPOCH
Efficacy: Progression Free Survival Rate14.5 (7.5 to 22.2)
SecondaryEfficacy: Event Free Survival

Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy. Events defined as start of new treatment, progression, or death.

Time frame:
up to 2 years after completion of treatment
Reported as:
Median · months
Efficacy: Event Free Survival
monthsNivo and EPOCH
Efficacy: Event Free Survival10.5 (6.9 to 20.5)
SecondaryImmune-related Predictors of Response

We assessed PD-L1 expression using immunohistochemistry on pre-treatment tumor tissue. The outcome of measurement was complete response yes vs. no. Using logistic regression, we assessed if the percentage of PDL1+ cells was predictive of achieving a complete response.

Time frame:
Within 6 months of treatment
Reported as:
Number · odds ratio
Immune-related Predictors of Response
odds ratioNivo and EPOCH
Immune-related Predictors of Response0.985 (0.938 to 1.034)

Adverse events

Collected over up to 100 days after last dose of nivolumab. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Nivolumab and EPOCH0/18 (0%)13/18 (72.2%)18/18 (100%)
Most frequent serious events
Showing 10 of 31
Most frequent serious events
EventNivolumab and EPOCH
Febrile NeutropeniaBlood and lymphatic system disorders3/18
Respiratory FailureRespiratory, thoracic and mediastinal disorders3/18
SepsisInfections and infestations3/18
EncephalopathyNervous system disorders2/18
Clostridioides difficileGastrointestinal disorders2/18
HypoxiaRespiratory, thoracic and mediastinal disorders2/18
Abdominal PainGastrointestinal disorders1/18
Atrial fibrillationCardiac disorders1/18
ThrombocytopeniaBlood and lymphatic system disorders1/18
DehydrationGeneral disorders1/18
Most frequent other events
Showing 10 of 190
Most frequent other events
EventNivolumab and EPOCH
neuropathyNervous system disorders11/18
EdemaGeneral disorders10/18
NauseaGastrointestinal disorders10/18
ConstipationGastrointestinal disorders9/18
DiarrheaGastrointestinal disorders9/18
PainGeneral disorders9/18
FatigueGeneral disorders8/18
FeverGeneral disorders8/18
AnemiaBlood and lymphatic system disorders7/18
ChillsGeneral disorders7/18

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Nivolumab and EPOCH
<=18 years0
Between 18 and 65 years9
>=65 years9
Age, Continuous
Age, Continuous(years)Nivolumab and EPOCH
Mean63.16 ± 10.43
Sex: Female, Male
Sex: Female, Male(Participants)Nivolumab and EPOCH
Female7
Male11
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Nivolumab and EPOCH
Hispanic or Latino5
Not Hispanic or Latino13
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Nivolumab and EPOCH
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White16
More than one race0
Unknown or Not Reported2
Region of Enrollment
Region of Enrollment(participants)Nivolumab and EPOCH
United States18
08

Study locations

3 sites
  • City of Hope Cancer Center
    Duarte, California 91010, United States
  • University of Colorado Hospital
    Aurora, Colorado 80045, United States
  • Thomas Jefferson University
    Philadelphia, Pennsylvania 19107, United States
09

References and documents

Publications

  • Schmitz N, Trumper L, Ziepert M, Nickelsen M, Ho AD, Metzner B, Peter N, Loeffler M, Rosenwald A, Pfreundschuh M. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. Blood. 2010 Nov 4;116(18):3418-25. doi: 10.1182/blood-2010-02-270785. Epub 2010 Jul 21. PubMed 20660290 ↗
  • Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008 Sep 1;26(25):4124-30. doi: 10.1200/JCO.2008.16.4558. Epub 2008 Jul 14. PubMed 18626005 ↗
  • Ellin F, Landstrom J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood. 2014 Sep 4;124(10):1570-7. doi: 10.1182/blood-2014-04-573089. Epub 2014 Jul 8. PubMed 25006130 ↗
  • Maeda Y, Nishimori H, Yoshida I, Hiramatsu Y, Uno M, Masaki Y, Sunami K, Masunari T, Nawa Y, Yamane H, Gomyo H, Takahashi T, Yano T, Matsuo K, Ohshima K, Nakamura S, Yoshino T, Tanimoto M. Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Haematologica. 2017 Dec;102(12):2097-2103. doi: 10.3324/haematol.2017.167742. Epub 2017 Sep 29. PubMed 28971899 ↗
  • Dunleavy K, Pittaluga S, Shovlin M, Roschewski M, Lai C, Steinberg SM, Jaffe ES, Wilson WH. Phase II trial of dose-adjusted EPOCH in untreated systemic anaplastic large cell lymphoma. Haematologica. 2016 Jan;101(1):e27-9. doi: 10.3324/haematol.2015.131151. Epub 2015 Oct 30. No abstract available. PubMed 26518748 ↗
  • Ghafouri S, Fenerty K, Schiller G, de Vos S, Eradat H, Timmerman J, Larson S, Mead M. Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience. Clin Lymphoma Myeloma Leuk. 2021 Dec;21(12):861-872. doi: 10.1016/j.clml.2021.07.002. Epub 2021 Jul 19. PubMed 34389271 ↗

Study documents

  • Protocol, analysis plan and consent form · Nov 24, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 29, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03586999
Lead sponsor
University of Colorado, Denver
Collaborators
Bristol-Myers Squibb
Responsible party
Sponsor
First posted
Jul 16, 2018
Start date
Nov 7, 2018
Primary completion
May 26, 2021
Completion
Sep 20, 2022
Results posted
Oct 29, 2024
Last update
Oct 29, 2024

Study contacts

Brad Haverkos, MD
principal investigator · University of Colorado, Denver

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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