Combination Chemotherapy in Treating Patients With Lymphoma

NCT00002835 | Completed Phase 3

• 5 other identifiers: MDA DM95-121P30CA016672MDA-DM-95121NCI-V96-1010CDR0000065044
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lymphoma

Keywords

stage I grade 3 follicular lymphoma; stage I adult diffuse small cleaved cell lymphoma; stage I adult diffuse mixed cell lymphoma; stage I adult diffuse large cell lymphoma; stage I adult immunoblastic large cell lymphoma; stage III grade 3 follicular lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV grade 3 follicular lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; contiguous stage II grade 3 follicular lymphoma; contiguous stage II adult diffuse small cleaved cell lymphoma; contiguous stage II adult diffuse mixed cell lymphoma; contiguous stage II adult immunoblastic large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma

Outcome Measures

Primary Outcomes (1)

• Efficacy of Early Intensification vs. Alternating Triple Chemotherapy

  Monthly

Study Arms (2)

Arm I

EXPERIMENTAL

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.

Biological: Filgrastim (G-CSF); Drug: Carmustine; Drug: Cytarabine (ARA-C); Drug: Etoposide (VP-16); Drug: Ifosfamide; Drug: Melphalan; Drug: mitoxantrone hydrochloride (DHAD); Procedure: Peripheral Blood Stem Cell Transplantation

Arm II

EXPERIMENTAL

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.

Biological: Bleomycin Sulfate (BLM); Biological: Recombinant Interferon Alfa; Drug: Cisplatin (CDDP); Drug: Cyclophosphamide; Drug: Idarubicin; Drug: Leucovorin Calcium; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Vincristine Sulfate; Procedure: Peripheral Blood Stem Cell Transplantation; Radiation: Radiation Therapy

Interventions

Bleomycin Sulfate (BLM) BIOLOGICAL

Also known as: Blenoxane, BLM

Arm II

Filgrastim (G-CSF) BIOLOGICAL

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.

Also known as: G-CSF, Neupogen

Arm I

Recombinant Interferon Alfa BIOLOGICAL

Arm II

Carmustine DRUG

Arm 1, Course 3, IV over 1 hour on day -6.

Also known as: BiCNU, BiCNUI

Arm I

Cisplatin (CDDP) DRUG

Also known as: Platinol, Platinol-AQ

Arm II

Cyclophosphamide DRUG

Also known as: Cytoxan, Neosar

Arm II

Cytarabine (ARA-C) DRUG

Arm 1, Course 3, every 12 hours on days -5 to -2.

Also known as: ARA-C, Cytosar, DepotCyt, Cytosine arabinosine hydrochloride

Arm I

Etoposide (VP-16) DRUG

Course 1, IV over 2 hours every 12 hours on days 1-3; Course 3, every 12 hours on days -5 to -2.

Also known as: VePesid

Arm I

Idarubicin DRUG

Also known as: Idamycin

Arm II

Ifosfamide DRUG

During Course 1, IV continuously; Course 2, IV continuously on days 1-3.

Also known as: Ifex

Arm I

Leucovorin Calcium DRUG

Also known as: Leucovorin, Citrovorum, Wellcovorin

Arm II

Melphalan DRUG

Also known as: Alkeran

Arm I

Methotrexate DRUG

Arm II

Methylprednisolone DRUG

Also known as: Depo-Medrol, Medrol, Solu-Medrol

Arm II

mitoxantrone hydrochloride (DHAD) DRUG

Arm 1, Course 2, IV on day 1.

Also known as: mitoxantrone, Novantrone

Arm I

Vincristine Sulfate DRUG

Arm II

Peripheral Blood Stem Cell Transplantation PROCEDURE

Infusion of stem cells on Day 0.

Also known as: autologous peripheral blood stem cells, PBSC

Arm I; Arm II

Radiation Therapy RADIATION

Also known as: RT

Arm II

Eligibility Criteria

• Age: 15 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Related Links

• UT MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic

Interventions

Bleomycin; Filgrastim; Granulocyte Colony-Stimulating Factor; Interferon-alpha; Carmustine; Cisplatin; Cyclophosphamide; Cytarabine; Etoposide; Idarubicin; Ifosfamide; Leucovorin; Melphalan; Methotrexate; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Mitoxantrone; Vincristine; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Interferon Type I; Interferons; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Oxazines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Aminopterin; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Anthraquinones; Anthrones; Anthracenes; Quinones; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Richard E. Champlin, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: April 16, 2003
• Study Start: October 30, 1995
• Primary Completion: February 4, 2004
• Study Completion: February 4, 2004
• Last Updated: November 15, 2018

Record last verified: 2018-11

Locations

US (1)