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

NCT ID: NCT00577993

Last Updated: 2020-11-16

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-03-16

Study Completion Date

2017-08-24

Brief Summary

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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

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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).

Conditions

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Lymphoma

Keywords

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Lymphoma Follicular Lymphoma Indolent Lymphoma Fludarabine Novantrone Mitoxantrone Decadron Dexamethasone Rituximab Anti-CD20 IDEC-C2B8 Chimeric Anti-CD20 Antibody Interferon Interferon Alpha-2b IFN Doxorubicin Vincristine Bleomycin Cyclophosphamide Etoposide Cisplatin Ara-C Methyl-Prednisolone Procarbazine Prednisone FND

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1: FND + Rituximab Followed by Interferon

Fludarabine/Novantrone/Decadron + Rituximab Followed by Interferon

Group Type ACTIVE_COMPARATOR

Fludarabine

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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.

2: FND Followed by Interferon & Rituximab

Fludarabine/Novantrone/Decadron Followed by Interferon \& Rituximab

Group Type ACTIVE_COMPARATOR

Fludarabine

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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.

3: CHOD-Bleo, ESHAP, NOPP + Rituximab Followed by Interferon

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

Group Type ACTIVE_COMPARATOR

Novantrone

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

25 mg/m\^2 IV Days 2 \& 3 of 1st Sequence.

Vincristine

Intervention Type DRUG

.7 mg/m\^2 IV Days 2 \& 3 of 1st Sequence; 1.4 mg/m\^2 IV Day 2 of 3rd Sequence.

Bleomycin

Intervention Type DRUG

5 unit/m\^2 IV Days 2 \& 3 of 1st Sequence.

Cyclophosphamide

Intervention Type DRUG

750 mg/m\^2 IV Day 2 of 1st Sequence.

Etoposide

Intervention Type DRUG

40 mg/m\^2 IV Days 1 through 4 of 2nd Sequence.

Cisplatin

Intervention Type DRUG

25 mg/m\^2 IV Days 1 through 4 of 2nd Sequence

Ara-C

Intervention Type DRUG

1.5 gm/m\^2 IV Day 5 of 2nd Sequence.

Methyl-Prednisolone

Intervention Type DRUG

500 mg IV Days 1 through 5 of 2nd Sequence.

Procarbazine

Intervention Type DRUG

100 mg/m\^2 PO Days 2 through 11 of 3rd Sequence.

Prednisone

Intervention Type DRUG

100 mg PO Days 1 through 5 of 3rd Sequence.

Interventions

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Fludarabine

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.

Intervention Type DRUG

Novantrone

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.

Intervention Type DRUG

Decadron

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.

Intervention Type DRUG

Rituximab

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.

Intervention Type DRUG

Interferon

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.

Intervention Type DRUG

Doxorubicin

25 mg/m\^2 IV Days 2 \& 3 of 1st Sequence.

Intervention Type DRUG

Vincristine

.7 mg/m\^2 IV Days 2 \& 3 of 1st Sequence; 1.4 mg/m\^2 IV Day 2 of 3rd Sequence.

Intervention Type DRUG

Bleomycin

5 unit/m\^2 IV Days 2 \& 3 of 1st Sequence.

Intervention Type DRUG

Cyclophosphamide

750 mg/m\^2 IV Day 2 of 1st Sequence.

Intervention Type DRUG

Etoposide

40 mg/m\^2 IV Days 1 through 4 of 2nd Sequence.

Intervention Type DRUG

Cisplatin

25 mg/m\^2 IV Days 1 through 4 of 2nd Sequence

Intervention Type DRUG

Ara-C

1.5 gm/m\^2 IV Day 5 of 2nd Sequence.

Intervention Type DRUG

Methyl-Prednisolone

500 mg IV Days 1 through 5 of 2nd Sequence.

Intervention Type DRUG

Procarbazine

100 mg/m\^2 PO Days 2 through 11 of 3rd Sequence.

Intervention Type DRUG

Prednisone

100 mg PO Days 1 through 5 of 3rd Sequence.

Intervention Type DRUG

Other Intervention Names

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2-fluoro-Ara Amp Mitoxantrone Dexamethasone Chimeric Anti-CD20 Antibody Anti-CD20 IDEC-C2B8 Interferon Alpha-2b IFN

Eligibility Criteria

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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
Maximum Eligible Age

76 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nathan Fowler, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

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http://www.mdanderson.org

The University of Texas M.D.Anderson Cancer Center

Other Identifiers

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NCI-2010-01566

Identifier Type: REGISTRY

Identifier Source: secondary_id

DM97-261

Identifier Type: -

Identifier Source: org_study_id