Phase I Trial of mBACOD and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in AIDS-Associated Large Cell, Immunoblastic, and Small Non-cleaved Lymphoma
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Lymphoma, Non-Hodgkin; HIV Infections
Intervention: Bleomycin sulfate (Drug); Vincristine sulfate (Drug); Doxorubicin hydrochloride (Drug); Cyclophosphamide (Drug); Methotrexate (Drug); Cytarabine (Drug); Leucovorin calcium (Drug); Sargramostim (Drug); Dexamethasone (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Walsh C, Study Chair Levine AM, Study Chair
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.
Clinical Details
Official title: Phase I Trial of mBACOD and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in AIDS-Associated Large Cell, Immunoblastic, and Small Non-cleaved Lymphoma
Study design: Masking: Open Label, Primary Purpose: Treatment
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.
Eligibility
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
USC CRS, Los Angeles, California 90033, United States
Additional Information
Related 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. 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.
Last updated: April 26, 2012
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