Combination Chemotherapy in Treating Patients With Lymphoma

November 13, 2018 updated by: M.D. Anderson Cancer Center

A Randomized Prospective Study of Early Intensification Versus Alternating Triple Therapy for Patients With Poor Prognosis Lymphoma

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of combination chemotherapy in treating patients who have intermediate-grade or immunoblastic lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the efficacy of early intensification vs alternating triple chemotherapy in patients with intermediate-grade or immunoblastic lymphoma with poor prognostic features.
  • Compare, in a prospective manner, the cost/benefit ratio of these regimens in these patients.
  • Determine the value of monitoring minimal residual disease detection via in vitro culture methods and polymerase chain reaction analysis of peripheral stem cell apheresis products and by longitudinal monitoring of blood and bone marrow samples in these patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to tumor score (3 or 4 vs 5 or 6).

During the first course of induction, patients receive IDSHAP comprising idarubicin (IDA) and cisplatin IV continuously on days 1-4, cytarabine (ARA-C) IV over 2 hours on day 5, and methylprednisolone (MePRDL) IV over 15 minutes on days 1-5. During the second course of induction, patients receive MBIDCOS comprising vincristine, bleomycin, and cyclophosphamide IV over 15 minutes on day 1, IDA IV continuously and MePRDL IV over 15 minutes on days 1-3, methotrexate (MTX) IV over 2 hours on day 10, and oral leucovorin calcium every 6 hours on days 11 and 12. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients with stable or responding disease after induction are randomized to 1 of 2 treatment arms.

Arm I

  • Patients receive the following 3 courses of early intensification.

    • First course: Patients receive ifosfamide (IFF) IV continuously and etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover and then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest.
    • Second course: Patients receive IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in the first course.
    • Third course: Patients receive carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity.

Arm II

  • Patients receive IDSHAP during courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Each course lasts 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients with residual disease after completion of arm I or II treatment undergo radiotherapy to areas of bulk disease if feasible. Patients on both arms with meningeal involvement receive ARA-C intrathecally (IT) alternated with MTX every other day until 1 week after clearing of CNS disease and then 2 IT injections during every course of chemotherapy thereafter. Patients with divergent histology who achieve complete response after completion of arm I or II treatment receive interferon alfa 3 times a week for 1 year.

Patients are followed at 1 month, every 3 months for 1 year, every 6 months for 1 year, and then annually for 2 years.

PROJECTED ACCRUAL: A maximum of 136 patients will be accrued for this study within 4 years.

Study Type

Interventional

Enrollment (Actual)

116

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030-4009
        • University of Texas - MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 59 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of previously untreated intermediate-grade or immunoblastic lymphoma

    • Tumor score of 3 or greater, defined by the presence of 3 or more of the following criteria :

      • Ann Arbor stage III or IV disease
      • B symptoms (fever, sweats, and weight loss greater than 10%)
      • At least 1 tumor mass greater than 7 cm or mediastinal mass visible on plain chest x-ray
      • Beta-2 microglobulin at least 3.0
      • Lactic dehydrogenase at least 1.1 times the upper limit of normal
  • T- and B-cell lymphomas allowed if intermediate grade or immunoblastic
  • Divergent histologies, including bone marrow involvement, allowed
  • CNS involvement allowed NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

  • 15 to 59

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin less than 2.0 mg/dL (unless elevation due to lymphoma)

Renal:

  • Creatinine no greater than 1.5 mg/dL (unless elevation due to lymphoma)

Cardiovascular:

  • LVEF greater than 50% by echocardiogram if over age 45
  • No congestive heart failure, angina, history of myocardial infarction, or arrhythmia unless cleared by principal investigator after cardiology consultation

Pulmonary:

  • No history of chronic obstructive or restrictive lung disease
  • Pulmonary consultation required for smokers or patients with questionable lung function

Other:

  • HIV negative
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No prior malignancy with poor prognosis (less than 90% probability of surviving for 5 years)
  • No geographic, economic, emotional, or social condition that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior biologic therapy

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • No prior endocrine therapy

Radiotherapy

  • No prior radiotherapy

Surgery

  • Not specified

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I

3 courses of early intensification:

First course: Ifosfamide (IFF) IV continuously and Etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest.

Second course: IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in first course.

Third course: Carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Melphalan
Other Names:
  • Alkeran
Procedure: Peripheral Blood Stem Cell Transplantation
Infusion of stem cells on Day 0.
Other Names:
  • PBSC
  • autologous peripheral blood stem cells
Biological: Filgrastim (G-CSF)
Arm 1: Administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover through Course 1 then 2 courses administered before PBSC harvest and same regimen with Course 2, then daily with Day 0 of infusion.
Other Names:
  • G-CSF
  • Neupogen
Drug: Carmustine
Arm 1, Course 3, IV over 1 hour on day -6.
Other Names:
  • BiCNU
  • BiCNUI
Drug: Cytarabine (ARA-C)
Arm 1, Course 3, every 12 hours on days -5 to -2.
Other Names:
  • Cytosar
  • ARA-C
  • DepotCyt
  • Cytosine arabinosine hydrochloride
Drug: Etoposide (VP-16)
Course 1, IV over 2 hours every 12 hours on days 1-3; Course 3, every 12 hours on days -5 to -2.
Other Names:
  • VePesid
Drug: Ifosfamide
During Course 1, IV continuously; Course 2, IV continuously on days 1-3.
Other Names:
  • Ifex
Drug: mitoxantrone hydrochloride (DHAD)
Arm 1, Course 2, IV on day 1.
Other Names:
  • Novantrone
  • mitoxantrone
Experimental: Arm II
IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7.
Drug: Methotrexate
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
  • Neosar
Drug: Methylprednisolone
Other Names:
  • Depo-Medrol
  • Medrol
  • Solu-Medrol
Radiation: Radiation Therapy
Other Names:
  • RT
Drug: Idarubicin
Other Names:
  • Idamycin
Drug: Leucovorin Calcium
Other Names:
  • Leucovorin
  • Wellcovorin
  • Citrovorum
Drug: Vincristine Sulfate
Procedure: Peripheral Blood Stem Cell Transplantation
Infusion of stem cells on Day 0.
Other Names:
  • PBSC
  • autologous peripheral blood stem cells
Biological: Bleomycin Sulfate (BLM)
Other Names:
  • BLM
  • Blenoxane
Biological: Recombinant Interferon Alfa
Drug: Cisplatin (CDDP)
Other Names:
  • Platinol
  • Platinol-AQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy of Early Intensification vs. Alternating Triple Chemotherapy
Time Frame: Monthly
Monthly

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 1995

Primary Completion (Actual)

February 4, 2004

Study Completion (Actual)

February 4, 2004

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

April 15, 2003

First Posted (Estimate)

April 16, 2003

Study Record Updates

Last Update Posted (Actual)

November 15, 2018

Last Update Submitted That Met QC Criteria

November 13, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MDA DM95-121
  • P30CA016672 (U.S. NIH Grant/Contract)
  • MDA-DM-95121 (Other Identifier: UT MD Anderson Cancer Center)
  • NCI-V96-1010
  • CDR0000065044 (Registry Identifier: NCI PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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