A Phase 2 interventional study of rituximab and tositumomab in Lymphoma, sponsored by SWOG Cancer Research Network. Completed at 114 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-08-28.
Sponsored by SWOG Cancer Research Network · Phase 2, Interventional, and Treatment
RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving a radiolabeled monoclonal antibody together with rituximab and combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying the side effects of giving iodine I 131 tositumomab together with rituximab and combination chemotherapy and to see how well it works in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.
OBJECTIVES:
OUTLINE: This is a multicenter study.
NOTE: *Patients receive R-CHOP in courses 1-4 and CHOP alone in courses 5 and 6.
After completion of maintenance therapy, patients are followed annually for up to 7 years. Patients who do not complete maintenance therapy are followed every 6 months for 2 years and then annually for up to 7 years.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 87 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →SWOG Cancer Research Network is the lead sponsor of 328 studies on the registry; 37 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Histologically confirmed* grade 1, 2, or 3 follicular B-cell non-Hodgkin lymphoma meeting the following criteria:
Patient must have unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 Cycles Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody. Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration.
Biological: rituximab · Biological: tositumomab · Drug: cyclophosphamide · Drug: doxorubicin · Drug: prednisone · Drug: vincristine · Radiation: tositumomab
Also known as: iodine I 131 tositumomab
Percentage of Participants With 3-year Progression-free Survival (PFS)
Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node \> 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is \> 1.5 cm, or if the both the long and short axes are \> 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.
Time frame: 0-3 years
5-year Progression-free Survival
Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node \> 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is \> 1.5 cm, or if the both the long and short axes are \> 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.
Time frame: 0-5 years
5-year Overall Survival
Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact.
Time frame: 0-5 years
Response Rate
Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of the following. Positron emission tomography (PET) must be negative if no pre-treatment PET scan or when the PET was positive before therapy. If the PET scan was negative before therapy, all nodal masses must have regressed. no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. PR is ≥ 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD. In patients with no pre-treatment PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.
Time frame: up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time frame: up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression.
| Milestone | R-CHOP+I-131 Tositumomab | Rituximab Maintenance |
|---|---|---|
| Started | 87 | 0 |
| Eligible and evaluable | 84 | 0 |
| Completed | 73 | 0 |
| Not completed | 14 | 0 |
| Withdrew: Adverse event | 3 | 0 |
| Withdrew: Refusal unrelated to adverse event | 6 | 0 |
| Withdrew: Other reason not protocol specified | 2 | 0 |
| Withdrew: Ineligible | 2 | 0 |
| Withdrew: No protocol treatment given | 1 | 0 |
| Milestone | R-CHOP+I-131 Tositumomab | Rituximab Maintenance |
|---|---|---|
| Started | 0 | 71 |
| Eligible and evaluable | 0 | 69 |
| Completed | 0 | 41 |
| Not completed | 0 | 30 |
| Withdrew: Adverse event | 0 | 10 |
| Withdrew: Refusal unrelated to adverse event | 0 | 8 |
| Withdrew: Progression/relapse | 0 | 1 |
| Withdrew: Death | 0 | 2 |
| Withdrew: Other reason not protocol specified | 0 | 7 |
| Withdrew: Ineligible | 0 | 2 |
Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node \> 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is \> 1.5 cm, or if the both the long and short axes are \> 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.
| percentage of participants | R-CHOP+I-131 Tositumomab Followed by Rituximab Maintenance |
|---|---|
| Percentage of Participants With 3-year Progression-free Survival (PFS) | 90 (81.9 to 95.1) |
Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node \> 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is \> 1.5 cm, or if the both the long and short axes are \> 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.
| percentage of participants | R-CHOP+I-131 Tositumomab Followed by Rituximab Maintenance |
|---|---|
| 5-year Progression-free Survival | 85 (74.8 to 90.7) |
Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact.
| percentage of participants | R-CHOP+I-131 Tositumomab Followed by Rituximab Maintenance |
|---|---|
| 5-year Overall Survival | 94 (86.3 to 97.5) |
Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of the following. Positron emission tomography (PET) must be negative if no pre-treatment PET scan or when the PET was positive before therapy. If the PET scan was negative before therapy, all nodal masses must have regressed. no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. PR is ≥ 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD. In patients with no pre-treatment PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.
| Participants | R-CHOP+I-131 Tositumomab Followed by Rituximab Maintenance |
|---|---|
| Complete Response | 61 |
| Patital Response | 22 |
| Assessment Inadequate | 1 |
Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
| Participants | R-CHOP+I-131 Tositumomab | Rituximab Maintenance |
|---|---|---|
| Albumin, serum-low (hypoalbuminemia) | 1 | 0 |
| Allergic reaction/hypersensitivity | 2 | 0 |
| Anorexia | 1 | 0 |
| Cough | 1 | 1 |
| Diarrhea | 1 | 0 |
| Dyspnea (shortness of breath) | 1 | 0 |
| Enteritis (inflammation of the small bowel) | 0 | 1 |
| Fatigue (asthenia, lethargy, malaise) | 8 | 1 |
| Febrile neutropenia | 14 | 0 |
| Fever in absence of neutropenia, ANC lt1.0x10e9/L | 2 | 0 |
| Glucose, serum-high (hyperglycemia) | 4 | 0 |
| Hemoglobin | 6 | 0 |
| Hypotension | 2 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Bladder | 1 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 1 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Catheter-rel | 1 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Dental-tooth | 1 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Lung | 1 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Lymphatic | 2 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Pharynx | 1 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Skin | 1 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - UTI | 1 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway | 1 | 0 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Wound | 1 | 0 |
| Inf w/normal ANC or Gr 1-2 neutrophils - Mid ear | 0 | 1 |
| Inf w/normal ANC or Gr 1-2 neutrophils - Sinus | 0 | 1 |
| Left ventricular systolic dysfunction | 1 | 1 |
| Leukocytes (total WBC) | 34 | 0 |
| Lymphopenia | 25 | 4 |
| Mood alteration - anxiety | 0 | 1 |
| Mood alteration - depression | 0 | 1 |
| Muscle weakness, not d/t neuropathy - body/general | 1 | 1 |
| Nasal cavity/paranasal sinus reactions | 0 | 1 |
| Nausea | 3 | 0 |
| Neuropathy: motor | 1 | 0 |
| Neuropathy: sensory | 6 | 0 |
| Neutrophils/granulocytes (ANC/AGC) | 48 | 1 |
| Opportunistic inf associated w/gt=Gr 2 lymphopenia | 1 | 0 |
| Pain - Abdomen NOS | 1 | 0 |
| Pain - Bone | 1 | 0 |
| Pain - Head/headache | 1 | 0 |
| Pain - Muscle | 1 | 0 |
| Pain-Other (Specify) | 0 | 1 |
| Platelets | 17 | 0 |
| Pulmonary hypertension | 0 | 1 |
| Restrictive cardiomyopathy | 0 | 1 |
| Secondary Malignancy-poss rel to cancer Tx | 0 | 1 |
| Sodium, serum-low (hyponatremia) | 1 | 0 |
| Syncope (fainting) | 1 | 0 |
| Thrombosis/thrombus/embolism | 1 | 0 |
| Valvular heart disease | 0 | 1 |
| Vasovagal episode | 0 | 1 |
| Vision-blurred vision | 1 | 0 |
| Vomiting | 2 | 0 |
| Weight loss | 1 | 0 |
Collected over up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| R-CHOP+I-131 Tositumomab | 0/84 (0%) | 0/84 (0%) | 84/84 (100%) |
| Rituximab Maintenance | 0/69 (0%) | 1/69 (1.4%) | 66/69 (95.7%) |
| Event | R-CHOP+I-131 Tositumomab | Rituximab Maintenance |
|---|---|---|
| Secondary Malignancy-poss rel to cancer TxNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/84 | 1/69 |
| Event | R-CHOP+I-131 Tositumomab | Rituximab Maintenance |
|---|---|---|
| Fatigue (asthenia, lethargy, malaise)General disorders | 70/84 | 42/69 |
| Leukocytes (total WBC)Investigations | 60/84 | 31/69 |
| NauseaGastrointestinal disorders | 58/84 | 16/69 |
| PlateletsInvestigations | 58/84 | 26/69 |
| HemoglobinBlood and lymphatic system disorders | 56/84 | 18/69 |
| Neutrophils/granulocytes (ANC/AGC)Investigations | 56/84 | 9/69 |
| Neuropathy: sensoryNervous system disorders | 48/84 | 15/69 |
| Hair loss/Alopecia (scalp or body)Skin and subcutaneous tissue disorders | 46/84 | 3/69 |
| ConstipationGastrointestinal disorders | 40/84 | 9/69 |
| LymphopeniaInvestigations | 36/84 | 32/69 |
Only eligible and evaluable patients were included in the analysis.
| Age, Continuous(years) | R-CHOP+I-131 Tositumomab |
|---|---|
| Median | 52.3 (28.9 to 79.9) |
| Sex: Female, Male(Participants) | R-CHOP+I-131 Tositumomab |
|---|---|
| Female | 44 |
| Male | 40 |
| Ethnicity (NIH/OMB)(Participants) | R-CHOP+I-131 Tositumomab |
|---|---|
| Hispanic or Latino | 2 |
| Not Hispanic or Latino | 81 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | R-CHOP+I-131 Tositumomab |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 1 |
| Black or African American | 3 |
| White | 78 |
| More than one race | 0 |
| Unknown or Not Reported | 2 |
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