Overview

This trial is active, not recruiting.

Condition lymphoma
Treatments rituximab, tositumomab, cyclophosphamide, doxorubicin, prednisone, vincristine
Phase phase 2
Target CD20
Sponsor Southwest Oncology Group
Collaborator National Cancer Institute (NCI)
Start date April 2009
End date December 2016
Trial size 87 participants
Trial identifier NCT00770224, CDR0000615104, S0801, U10CA032102

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
rituximab
tositumomab
cyclophosphamide
doxorubicin
prednisone
vincristine
tositumomab iodine I 131 tositumomab

Primary Outcomes

Measure
3-year progression-free survival (PFS)
time frame: 0-3 years

Secondary Outcomes

Measure
5-year Progression-free Survival
time frame: 0-5 years
5-year overall survival
time frame: 0-5 years
Response rate
time frame: up to 1 year while on treatment, or up to maximum of 7 years on protocol, or time of disease progression
Safety profile as assessed by NCI CTCAE v4.0
time frame: up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed* grade 1, 2, or 3 follicular B-cell non-Hodgkin lymphoma meeting the following criteria: - Bulky stage II or stage III or IV disease - Diffuse large cell component must be < 25% of the biopsy - Confirmed cluster of differentiation antigen 20 (CD20) antigen-positive disease NOTE: *Needle aspiration or cytology are not considered adequate for pathology review - Patient must have unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days - Positive biopsy performed > 42 days but < 6 months allowed - Previously untreated disease - Bidimensionally measurable disease - No clinical evidence of central nervous system (CNS) involvement by lymphoma PATIENT CHARACTERISTICS: - Zubrod performance status 0-2 - Cardiac ejection fraction ≥ 45% by multigated acquisition scan (MUGA) or ECHO - No significant cardiac abnormalities - No known HIV positivity - No requirement for continuous supplemental oxygen therapy - No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer from which the patient is currently in complete remission - Not pregnant or nursing - Fertile patients must use effective contraception during and for 12 months after completion of maintenance therapy PRIOR CONCURRENT THERAPY: - No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma - No prior solid organ transplantation

Additional Information

Official title A Phase II Study of Iodine-131-Labeled Tositumomab in Combination With Cyclophosphamide, Doxorubicin, Vincristine, Prednisone and Rituximab Therapy for Patients With Advanced Stage Follicular Non-Hodgkin's Lymphoma
Description OBJECTIVES: - To evaluate the response rate in patients with previously untreated stage II-IV follicular non-Hodgkin lymphoma treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) in combination with iodine I 131 tositumomab. - To evaluate the toxicity of this regimen in these patients. - To estimate the 3-year progression-free survival rate in patients treated with this regimen. - To estimate the 5-year progression-free and overall survival rate in patients treated with this regimen. - To assess the safety profile of this regimen in these patients. OUTLINE: This is a multicenter study. - Induction therapy: Patients receive R-CHOP* comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with at least stable disease then proceed to consolidation therapy. NOTE: *Patients receive R-CHOP in courses 1-4 and CHOP alone in courses 5 and 6. - Consolidation therapy: Within 12 weeks after completion of induction therapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo whole body gamma camera scans over a 1-week period to determine the rate of total body clearance of radioactivity and the therapeutic dose of iodine I 131 tositumomab. Within 7-14 days after the dosimetric dose, patients receive tositumomab IV over 1 hour followed by a therapeutic dose of iodine I 131 tositumomab IV over 20 minutes. Patients with at least stable disease then proceed to maintenance therapy. - Maintenance therapy: Beginning approximately 1 year after study entry and no more than 28 days after restaging, patients receive rituximab IV every 3 months for up to 4 years (16 courses) in the absence of disease progression or unacceptable toxicity. 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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Southwest Oncology Group.