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

Fludarabine, Mitoxantrone, and Dexamethasone (FND) Plus Chimeric Anti-CD20 Monoclonal Antibody (Rituximab) for Stage IV Indolent Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Fludarabine; Drug: Novantrone; Drug: Decadron; Drug: Rituximab; Drug: Interferon; Drug: Doxorubicin; Drug: Vincristine; Drug: Bleomycin; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Cisplatin; Drug: Ara-C; Drug: Methyl-Prednisolone; Drug: Procarbazine; Drug: Prednisone

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).

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 76 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1: FND + Rituximab Followed by Interferon; Fludarabine/Novantrone/Decadron + Rituximab Followed by Interferon	Drug: 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.; Other Names: 2-fluoro-Ara Amp; 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.; Other Names: Mitoxantrone; 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.; Other Names: Dexamethasone; 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.; Other Names: Chimeric Anti-CD20 Antibody; IDEC-C2B8; Anti-CD20; 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.; Other Names: Interferon Alpha-2b; IFN
Active Comparator: 2: FND Followed by Interferon & Rituximab; Fludarabine/Novantrone/Decadron Followed by Interferon & Rituximab	Drug: 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.; Other Names: 2-fluoro-Ara Amp; 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.; Other Names: Mitoxantrone; 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.; Other Names: Dexamethasone; 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.; Other Names: Chimeric Anti-CD20 Antibody; IDEC-C2B8; Anti-CD20; 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.; Other Names: Interferon Alpha-2b; IFN
Active Comparator: 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	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.; Other Names: Mitoxantrone; 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.; Other Names: Dexamethasone; 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.; Other Names: Chimeric Anti-CD20 Antibody; IDEC-C2B8; Anti-CD20; 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.; Other Names: Interferon Alpha-2b; IFN; Drug: Doxorubicin; 25 mg/m^2 IV Days 2 & 3 of 1st Sequence.; Drug: Vincristine; .7 mg/m^2 IV Days 2 & 3 of 1st Sequence; 1.4 mg/m^2 IV Day 2 of 3rd Sequence.; Drug: Bleomycin; 5 unit/m^2 IV Days 2 & 3 of 1st Sequence.; Drug: Cyclophosphamide; 750 mg/m^2 IV Day 2 of 1st Sequence.; Drug: Etoposide; 40 mg/m^2 IV Days 1 through 4 of 2nd Sequence.; Drug: Cisplatin; 25 mg/m^2 IV Days 1 through 4 of 2nd Sequence; Drug: Ara-C; 1.5 gm/m^2 IV Day 5 of 2nd Sequence.; Drug: Methyl-Prednisolone; 500 mg IV Days 1 through 5 of 2nd Sequence.; Drug: Procarbazine; 100 mg/m^2 PO Days 2 through 11 of 3rd Sequence.; Drug: Prednisone; 100 mg PO Days 1 through 5 of 3rd Sequence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Overall Survival (10 Years) by Treatment	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.	10 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progression Free Survival (10 Years) by Treatment	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.	10 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Genentech, Inc.

Publications and helpful links

Helpful Links

• The University of Texas M.D.Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 1998
• Primary Completion (Actual): August 24, 2017
• Study Completion (Actual): August 24, 2017

Study Registration Dates

• First Submitted: December 18, 2007
• First Submitted That Met QC Criteria: December 18, 2007
• First Posted (Estimate): December 20, 2007

Study Record Updates

• Last Update Posted (Actual): November 16, 2020
• Last Update Submitted That Met QC Criteria: October 22, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Cisplatin; Lymphoma; Rituximab; Follicular Lymphoma; Cyclophosphamide; Ara-C; Etoposide; Dexamethasone; Doxorubicin; Vincristine; Interferon; Prednisone; Fludarabine; Decadron; Novantrone; Mitoxantrone; Bleomycin; Procarbazine; IFN; Indolent Lymphoma; Anti-CD20; IDEC-C2B8; Chimeric Anti-CD20 Antibody; Interferon Alpha-2b; Methyl-Prednisolone; FND
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Dexamethasone; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Interferons; Interferon-alpha; Cyclophosphamide; Etoposide; Interferon alpha-2; Rituximab; Prednisone; Doxorubicin; Fludarabine; Vincristine; Mitoxantrone; Bleomycin; Procarbazine
• Other Study ID Numbers: DM97-261; NCI-2010-01566 (Registry Identifier: NCI CTRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No