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Fludarabine, Mitoxantrone, and Dexamethasone (FND) Plus Rituximab for Lymphoma Patients

Registration Number
NCT00577993
Lead Sponsor
M.D. Anderson Cancer Center
Brief 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.

Detailed 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 University of Texas MD Anderson Cancer Center (UTMDACC).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
210
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2: FND Followed by Interferon & RituximabFludarabineFludarabine/Novantrone/Decadron Followed by Interferon \& Rituximab
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonInterferonCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
1: FND + Rituximab Followed by InterferonInterferonFludarabine/Novantrone/Decadron + Rituximab Followed by Interferon
2: FND Followed by Interferon & RituximabDecadronFludarabine/Novantrone/Decadron Followed by Interferon \& Rituximab
2: FND Followed by Interferon & RituximabInterferonFludarabine/Novantrone/Decadron Followed by Interferon \& Rituximab
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonMethyl-PrednisoloneCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
1: FND + Rituximab Followed by InterferonFludarabineFludarabine/Novantrone/Decadron + Rituximab Followed by Interferon
1: FND + Rituximab Followed by InterferonNovantroneFludarabine/Novantrone/Decadron + Rituximab Followed by Interferon
1: FND + Rituximab Followed by InterferonDecadronFludarabine/Novantrone/Decadron + Rituximab Followed by Interferon
1: FND + Rituximab Followed by InterferonRituximabFludarabine/Novantrone/Decadron + Rituximab Followed by Interferon
2: FND Followed by Interferon & RituximabNovantroneFludarabine/Novantrone/Decadron Followed by Interferon \& Rituximab
2: FND Followed by Interferon & RituximabRituximabFludarabine/Novantrone/Decadron Followed by Interferon \& Rituximab
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonNovantroneCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonDecadronCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonRituximabCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonDoxorubicinCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonBleomycinCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonVincristineCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonEtoposideCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonCyclophosphamideCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonCisplatinCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonAra-CCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonProcarbazineCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by InterferonPrednisoneCyclophosphamide/Vincristine/Doxorubicin/Bleomycin (1st Sequence) + Rituximab; Etoposide/Cisplatin/Ara-C/Methyl-Prednisol (2nd Sequence); Novantrone/Vincristine/Procarbazine/Prednisone + Rituximab (3rd Sequence) Followed by Interferon
Primary Outcome Measures
NameTimeMethod
Number of Participants With Overall Survival (10 Years) by Treatment10 Years

Overall Survival is the time from date of treatment start until date of death due to any cause or last Follow-up within 10 years.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Progression Free Survival (10 Years) by Treatment10 years

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Trial Locations

Locations (1)

University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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