Overview

This trial is active, not recruiting.

Condition lymphoma
Treatments fludarabine, novantrone, decadron, rituximab, interferon, doxorubicin, vincristine, bleomycin, cyclophosphamide, etoposide, cisplatin, ara-c, methyl-prednisolone, procarbazine, prednisone
Phase phase 3
Target CD20
Sponsor M.D. Anderson Cancer Center
Collaborator Genentech, Inc.
Start date March 1998
End date December 2017
Trial size 210 participants
Trial identifier NCT00577993, DM97-261, NCI-2010-01566

Summary

The goal of this clinical research study is to compare chemotherapy given with rituximab to chemotherapy followed by rituximab. The safety of both treatment schedules will be studied. Laboratory tests of genetic changes in blood and bone marrow before and during the study will also be monitored.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Fludarabine/Novantrone/Decadron + Rituximab Followed by Interferon
fludarabine 2-fluoro-Ara Amp
Group 1= 25 mg/m^2 IV over 15 min. Days 2 through 4 for 8 Cycles; Group 2 = 25 mg/m^2 IV over 15 min. Days 1 through 3 for 8 Cycles.
novantrone Mitoxantrone
Group 1 = 10 mg/m^2 IV over 15 min. Day 2 for 8 Cycles; Group 2 = 10 mg/m^2 IV over 15 min. Day 1 for 8 Cycles; Group 3 = 10 mg/m^2 IV over 15 min. Day 2 of 3rd Sequence.
decadron Dexamethasone
Group 1 = 20 mg IV over 15 min. Days 1 through 5 for 8 Cycles, then Days 1 through 3 Every Month for 1 Year; Group 2 = 20 mg IV over 15 min. Days 1 through 5 for 8 Cycles, then Days 1 through 3 Every Month for 1 Year; Group 3 = 40 mg PO Days 1 through 4 of 1st Sequence; After Completion of 3 Sequences, Days 1 through 3 Every Month for 1 Year.
rituximab Chimeric Anti-CD20 Antibody
Group 1 = 375 mg/m^2 IV Days 1 through 8 of Course 1, then Day 1 Only of Cycles 2 through 5; Group 2 = 4 Months after IFN Starts, 375 mg/m^2 IV Once Per Month for 6 Months; Group 3 = 375 mg/m^2 IV Days 1 through 8 of 1st Sequence; 375 mg/m^2 IV Days 1 through 8 of 3rd Sequence.
interferon Interferon Alpha-2b
Group 1 = After Completion of Fludarabine, Novantrone, & Rituximab, IFN 3 mcg/ml/m^2 SQ Days 1 through 14 Each Month for 1 year; Group 2 = After Completion of Fludarabine & Novantrone, IFN 3 mcg/ml/m^2 SQ Days 1 through 14 Each Month for 1 year; Group 3 = After Completion of 3 Sequences, IFN 3 mcg/ml/m^2 SQ Days 1 through 14 Each Month for 1 year.
(Active Comparator)
Fludarabine/Novantrone/Decadron Followed by Interferon & Rituximab
fludarabine 2-fluoro-Ara Amp
Group 1= 25 mg/m^2 IV over 15 min. Days 2 through 4 for 8 Cycles; Group 2 = 25 mg/m^2 IV over 15 min. Days 1 through 3 for 8 Cycles.
novantrone Mitoxantrone
Group 1 = 10 mg/m^2 IV over 15 min. Day 2 for 8 Cycles; Group 2 = 10 mg/m^2 IV over 15 min. Day 1 for 8 Cycles; Group 3 = 10 mg/m^2 IV over 15 min. Day 2 of 3rd Sequence.
decadron Dexamethasone
Group 1 = 20 mg IV over 15 min. Days 1 through 5 for 8 Cycles, then Days 1 through 3 Every Month for 1 Year; Group 2 = 20 mg IV over 15 min. Days 1 through 5 for 8 Cycles, then Days 1 through 3 Every Month for 1 Year; Group 3 = 40 mg PO Days 1 through 4 of 1st Sequence; After Completion of 3 Sequences, Days 1 through 3 Every Month for 1 Year.
rituximab Chimeric Anti-CD20 Antibody
Group 1 = 375 mg/m^2 IV Days 1 through 8 of Course 1, then Day 1 Only of Cycles 2 through 5; Group 2 = 4 Months after IFN Starts, 375 mg/m^2 IV Once Per Month for 6 Months; Group 3 = 375 mg/m^2 IV Days 1 through 8 of 1st Sequence; 375 mg/m^2 IV Days 1 through 8 of 3rd Sequence.
interferon Interferon Alpha-2b
Group 1 = After Completion of Fludarabine, Novantrone, & Rituximab, IFN 3 mcg/ml/m^2 SQ Days 1 through 14 Each Month for 1 year; Group 2 = After Completion of Fludarabine & Novantrone, IFN 3 mcg/ml/m^2 SQ Days 1 through 14 Each Month for 1 year; Group 3 = After Completion of 3 Sequences, IFN 3 mcg/ml/m^2 SQ Days 1 through 14 Each Month for 1 year.
(Active Comparator)
Cyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
novantrone Mitoxantrone
Group 1 = 10 mg/m^2 IV over 15 min. Day 2 for 8 Cycles; Group 2 = 10 mg/m^2 IV over 15 min. Day 1 for 8 Cycles; Group 3 = 10 mg/m^2 IV over 15 min. Day 2 of 3rd Sequence.
decadron Dexamethasone
Group 1 = 20 mg IV over 15 min. Days 1 through 5 for 8 Cycles, then Days 1 through 3 Every Month for 1 Year; Group 2 = 20 mg IV over 15 min. Days 1 through 5 for 8 Cycles, then Days 1 through 3 Every Month for 1 Year; Group 3 = 40 mg PO Days 1 through 4 of 1st Sequence; After Completion of 3 Sequences, Days 1 through 3 Every Month for 1 Year.
rituximab Chimeric Anti-CD20 Antibody
Group 1 = 375 mg/m^2 IV Days 1 through 8 of Course 1, then Day 1 Only of Cycles 2 through 5; Group 2 = 4 Months after IFN Starts, 375 mg/m^2 IV Once Per Month for 6 Months; Group 3 = 375 mg/m^2 IV Days 1 through 8 of 1st Sequence; 375 mg/m^2 IV Days 1 through 8 of 3rd Sequence.
interferon Interferon Alpha-2b
Group 1 = After Completion of Fludarabine, Novantrone, & Rituximab, IFN 3 mcg/ml/m^2 SQ Days 1 through 14 Each Month for 1 year; Group 2 = After Completion of Fludarabine & Novantrone, IFN 3 mcg/ml/m^2 SQ Days 1 through 14 Each Month for 1 year; Group 3 = After Completion of 3 Sequences, IFN 3 mcg/ml/m^2 SQ Days 1 through 14 Each Month for 1 year.
doxorubicin
25 mg/m^2 IV Days 2 & 3 of 1st Sequence.
vincristine
.7 mg/m^2 IV Days 2 & 3 of 1st Sequence; 1.4 mg/m^2 IV Day 2 of 3rd Sequence.
bleomycin
5 unit/m^2 IV Days 2 & 3 of 1st Sequence.
cyclophosphamide
750 mg/m^2 IV Day 2 of 1st Sequence.
etoposide
40 mg/m^2 IV Days 1 through 4 of 2nd Sequence.
cisplatin
25 mg/m^2 IV Days 1 through 4 of 2nd Sequence
ara-c
1.5 gm/m^2 IV Day 5 of 2nd Sequence.
methyl-prednisolone
500 mg IV Days 1 through 5 of 2nd Sequence.
procarbazine
100 mg/m^2 PO Days 2 through 11 of 3rd Sequence.
prednisone
100 mg PO Days 1 through 5 of 3rd Sequence.

Primary Outcomes

Measure
To study and compare molecular response rates with the FND regimen followed by rituximab (chimeric anti-CD20 antibody) and interferon versus FND plus rituximab concurrently, followed by interferon
time frame: 10 Years
To study the toxicity of these two regimens, including their effects on B- and T- cell subsets, immunoglobulins, and patterns of infections.
time frame: 10 Years

Secondary Outcomes

Measure
Compare failure-free and overall survival rates
time frame: 10 Years
To identify and treat with a separate strategy those follicular lymphoma patients without bcl-2 mbr or mcr gene rearrangement ("germline" patients)
time frame: 10 Years

Eligibility Criteria

Male or female participants up to 76 years old.

Inclusion Criteria: 1. Previously untreated stage IV indolent B-cell lymphoma [Amendment May 2001: eligibility restricted to follicular lymphoma] 2. Age <76 Exclusion Criteria: N/A

Additional Information

Official title Fludarabine, Mitoxantrone, and Dexamethasone (FND) Plus Chimeric Anti-CD20 Monoclonal Antibody (Rituximab) for Stage IV Indolent Lymphoma
Principal investigator Nathan Fowler, MD
Description Rituximab is a monoclonal antibody that is designed to attach to leukemia cells and activate a series of events that may cause the cancer cells to die. Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying. Mitoxantrone is designed to stop cancer cells from making DNA, which may stop the cells from making more cells. Dexamethasone is a corticosteroid that is similar to a natural hormone made by your body. Dexamethasone is often given to MM patients in combination with other chemotherapy to treat cancer. Study Groups: If you are found eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. Each group will receive 8 "cycles" of treatment. One (1) cycle will last 28 days. Group 1: If you are in Group 1, you will receive the following drugs at the following times. Each study cycle is 28 days: - Rituximab will be given through a needle in the vein over about 90 minutes on Days 1 and 8 of the first course Cycle 1, and on Day 1 only of Cycles 2-5 of Fludarabine/ Mitoxantrone/ Dexamethasone (FND) treatment. - Fludarabine will be given through a needle in the vein over about 15 minutes on Days 2-4 of each cycle. - Mitoxantrone will be given through a needle in the vein over about 15 minutes on Day 2 of each cycle. - You will take dexamethasone by mouth with water on Days 1-5 of each 28-day cycle (FND). If you miss any doses of the study drugs, please contact the research staff for instructions. You will not receive rituximab in Cycles 6-8. When the 8 cycles are finished, you will begin receiving the drug interferon on Days 1-14 each month for 1 year. Dexamethasone will be given on Days 1-3 every month for 1 year. Patients in group 2 will receive fludarabine on Days 1-3, mitoxantrone on Day 1, and dexamethasone on Days 1-5 of each 28-day cycle. When 8 cycles of treatment are finished, patients will begin receiving the drug interferon on Days 1-14 each month for 1 year. Dexamethasone will be given on Days 1-3 every month for 1 year. About 4 months after interferon treatment starts, patients in group 2 will begin receiving rituximab once a month for 6 months. Other drugs may be given to help decrease the risk of or ease side effects. Treatment may be delayed or stopped if side effects are severe. Most of the drugs are given by vein. A catheter (a tube) will be placed in a vein to decrease the number of needle sticks. Dexamethasone may be taken by mouth instead of given by vein. Some patients in this study, with changes in certain genes will receive different chemotherapy drugs than other patients in the study will. The patients will, like all the other patients, receive rituximab and interferon. But instead of the FND chemotherapy regimen, they will receive a sequence of three regimens, CHOD-Bleo, ESHAP, and NOPP. The drugs in these regimens include: cyclophosphamide, doxorubicin, vincristine, bleomycin, VP-16, Ara-C, cisplatin, mitoxantrone, procarbazine, and corticosteroids (prednisone, methylprednisolone, dexamethasone). During the study, patients will have blood tests every week. Complete exams will be given in Cycles 2 and 4; patients will return to the clinic for these. Every 2 or 3 cycles, patients will have a chest x-ray and CT scans of the abdomen and pelvis. Bone marrow samples will be taken. Heart function tests (EKG) will be done as needed. After the study ends, patients will return for checkups every 3 months in the first year, every 4 months in years 2 and 3, and every 6 months in years 4 and 5. After that, checkups will be needed once a year. Blood and bone marrow samples will be taken at these visits. This is an investigational study. Rituximab is approved by FDA for commercial use. The other drugs used in the study are also approved for commercial use. About 210 patients will take part in the study. All will be enrolled at UTMDACC.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.