Phase I Trial of mBACOD and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in AIDS-Associated Large Cell, Immunoblastic, and Small Non-cleaved Lymphoma

NCT00000689 | Completed Phase 1

• 2 other identifiers: ACTG 07411048
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the toxicity and effectiveness of adding sargramostim (recombinant granulocyte-macrophage colony stimulating factor; GM-CSF) to a standard chemotherapy drug combination (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) known as mBACOD in the treatment of non-Hodgkin's lymphoma in patients who are infected with HIV. Treatment of patients with AIDS-associated lymphoma is achieving inferior results when compared with outcomes for non-AIDS patients. Treatment with mBACOD has been promising, but the toxicity is very high. Patients treated with mBACOD have very low white blood cell counts. GM-CSF has increased the number of white blood cells in animal studies and preliminary human studies. It is hoped that including GM-CSF among the drugs given to lymphoma patients will prevent or lessen the decrease in white blood cells caused by mBACOD.

Conditions

Lymphoma, Non-Hodgkin; HIV Infections

Keywords

M-BACOD protocol; Nervous System Neoplasms; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Cytarabine; Drug Evaluation; Drug Therapy, Combination; Granulocyte-Macrophage Colony-Stimulating Factor; Administration, Oral; Acquired Immunodeficiency Syndrome; Antineoplastic Agents, Combined

Interventions

Bleomycin sulfate DRUG

Vincristine sulfate DRUG

Doxorubicin hydrochloride DRUG

Cyclophosphamide DRUG

Methotrexate DRUG

Cytarabine DRUG

Leucovorin calcium DRUG

Sargramostim DRUG

Dexamethasone DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have:
• Positive HIV antibody by ELISA with Western blot confirmation, or positive HIV culture or serum p24 antigen capture assay, or prior diagnosis of AIDS by the CDC surveillance criteria.
• Pathological diagnosis of large cell (cleaved or non-cleaved), immunoblastic, or small non-cleaved lymphoma, stage I, II, III, or IV.
• If displaying systemic ("B") symptoms, evaluation for concurrent opportunistic infections as follows:
• Buffy coat for Mycobacterium intracellulare-avium (MAI) and cytomegalovirus (CMV) cultures; serum cryptococcal antigen; some measure of pulmonary function to exclude Pneumocystis carinii pneumonia including chest x-ray and either gallium scan, blood gases, or DLCO; stool culture and special stains for Salmonella, Isospora belli, cryptosporidium, CMV, and MAI in patients with diarrhea; computerized tomography (CT) scan or magnetic resonance imaging (MRI) of brain, or lumbar puncture for India ink, acid-fast bacilli smear, cryptococcal antigen, or fungal/mycobacterial culture.
• Bone marrow involvement is permitted if the patient meets the hematologic criteria above.
• Patients who have central nervous system (CNS) involvement at diagnosis or who are diagnosed during treatment will receive cranial radiotherapy:
• \- The total dose of 2400 rads will be delivered at a rate of 200 rads/day to the mid plane employing parallel opposing, lateral whole brain fields. The lower border of the field will encompass C2 to cover the meninges.
• Patients will be treated 5 days/week, Monday through Friday, until the total prescribed dose has been completed.
• Radiation will begin as soon as possible after documentation of lymphomatous disease in the CNS. If a second course of treatment is required, the 2400 rads is well within whole brain tolerance for normal tissues (4500-5000 rads).

You may not qualify if:

• Co-existing Condition:
• Patients with the following are excluded:
• Acute bacterial or opportunistic infection.
• Second primary cancer other than Kaposi's sarcoma, non-melanoma skin cancer, or carcinoma in-situ of the cervix.
• Primary central nervous system (CNS) lymphoma.
• Concurrent Medication:
• Excluded:
• Patients receiving prophylactic or maintenance therapy for bacterial or opportunistic infections, with the exception of those receiving Fansidar (sulfadoxine / pyrimethamine) for Pneumocystis carinii pneumonia prophylaxis.
• Antiretroviral agents.
• Immunomodulators.
• Patients with the following are excluded:
• Acute bacterial or opportunistic infection.
• Second primary cancer other than Kaposi's sarcoma, non-melanoma skin cancer, or carcinoma in-situ of the cervix.
• Primary central nervous system (CNS) lymphoma.
• Prior Medication:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

USC CRS

Los Angeles, California, 90033, United States

Location

Related Publications (2)

• Walsh C, Wernz JC, Levine A, Rarick M, Willson E, Melendez D, Bonnem E, Thompson J, Shelton B. Phase I trial of m-BACOD and granulocyte macrophage colony stimulating factor in HIV-associated non-Hodgkin's lymphoma. J Acquir Immune Defic Syndr (1988). 1993 Mar;6(3):265-71.

  PMID: 7680712 BACKGROUND

• Redfield RR, Birx DL, Ketter N, Tramont E, Polonis V, Davis C, Brundage JF, Smith G, Johnson S, Fowler A, et al. A phase I evaluation of the safety and immunogenicity of vaccination with recombinant gp160 in patients with early human immunodeficiency virus infection. Military Medical Consortium for Applied Retroviral Research. N Engl J Med. 1991 Jun 13;324(24):1677-84. doi: 10.1056/NEJM199106133242401.

  PMID: 1674589 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; HIV Infections; Nervous System Neoplasms; Acquired Immunodeficiency Syndrome

Interventions

Bleomycin; Vincristine; Doxorubicin; Cyclophosphamide; Methotrexate; Cytarabine; Leucovorin; sargramostim; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Neoplasms by Site; Nervous System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Officials

• Walsh C

  STUDY CHAIR

• Levine AM

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: March 1, 1991
• Last Updated: November 2, 2021

Record last verified: 2021-10

Locations

US (1)