- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000689
Phase I Trial of mBACOD and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in AIDS-Associated Large Cell, Immunoblastic, and Small Non-cleaved Lymphoma
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.
Study Overview
Status
Conditions
Detailed Description
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.
Patients admitted to the study receive chemotherapy in 21-day cycles. The length of therapy, 2 - 8 months, depends on how the tumor responds to treatment. Four medicines are given on day 1 of each cycle by vein (IV) (doxorubicin, cyclophosphamide, bleomycin, vincristine). Dosages of doxorubicin and cyclophosphamide are increased in later groups of patients if toxicity in the first group is tolerable. A fifth medicine (dexamethasone) is given by mouth (PO) on days 1 - 5 of each cycle and the sixth medicine (methotrexate) is given IV on day 15 of each cycle. Leucovorin is given after methotrexate to prevent methotrexate side effects. GM-CSF treatment is started on day 3 and continued for 11 days. To prevent the spread of the tumor, a spinal tap is done on 4 occasions to inject cytosine arabinoside directly into the spinal fluid. If tumor cells are present in the spinal fluid, the patient also takes cytosine arabinoside by spinal tap 3 x/week until the tumor cells disappear and then at monthly intervals for 1 year. Patients with tumor cells in the spinal fluid are also given radiation treatment to the head.
Study Type
Enrollment
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
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Los Angeles, California, United States, 90033
- USC CRS
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
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).
Exclusion Criteria
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:
Excluded:
- Prior therapy for lymphoma.
- Excluded within 1 week of study entry:
- Antiretroviral agents and immunomodulators.
Prior Treatment:
Excluded:
- Prior therapy for lymphoma.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Masking: None (Open Label)
Collaborators and Investigators
Investigators
- Study Chair: Walsh C
- Study Chair: Levine AM
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Lymphoma, Non-Hodgkin
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- 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
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Micronutrients
- Antibiotics, Antineoplastic
- Vitamins
- Reproductive Control Agents
- Antidotes
- Vitamin B Complex
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Dexamethasone
- Cyclophosphamide
- Leucovorin
- Levoleucovorin
- Doxorubicin
- Liposomal doxorubicin
- Cytarabine
- Methotrexate
- Vincristine
- Sargramostim
- Bleomycin
Other Study ID Numbers
- ACTG 074
- 11048 (Registry Identifier: DAIDS ES Registry Number)
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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