Clinical trial NCT00000801: Phase II Trial of Sequential Chemotherapy and Radiotherapy for AIDS-Related Primary Central Nervous System Lymphoma
Official title: Phase II Trial of Sequential Chemotherapy and Radiotherapy for AIDS-Related Primary Central Nervous System Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin
HIV Infections
Keywords: Vincristine
Cyclophosphamide
Cytarabine
Dexamethasone
Doxorubicin
Granulocyte Colony-Stimulating Factor
Combined Modality Therapy
Acquired Immunodeficiency Syndrome
Antineoplastic Agents, Combined
Brain Neoplasms
Lymphoma, High-Grade
Lymphoma, Intermediate-Grade
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 33
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To estimate the response rate, overall and disease-free survival, toxicities, factors associated with outcome, and effect on quality of life in patients with AIDS-related primary CNS lymphoma treated with CHOD (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) plus filgrastim (granulocyte-colony stimulating factor; G-CSF) and external beam irradiation. To determine other clinical markers present in this patient population.

Combined modality therapy may prove of benefit for patients with AIDS-related primary CNS lymphoma.

Detailed description: Combined modality therapy may prove of benefit for patients with AIDS-related primary CNS lymphoma.

Patients who upon staging workup are found to be without systemic involvement undergo one cycle of chemotherapy with cyclophosphamide, doxorubicin, vincristine, dexamethasone, and G-CSF. Cyclophosphamide, doxorubicin, and vincristine are administered intravenously on day 1. Dexamethasone is administered intravenously on day 1 and then orally thereafter with gradual discontinuation. G-CSF is administered subcutaneously daily beginning on day 2 and continuing for a total of 10 days or until blood counts have recovered to an acceptable level. Patients with evidence of cancer cells in their cerebrospinal fluid (CSF) will receive chemotherapy with intrathecal cytarabine twice weekly until no further evidence of cancer cells is found in the CSF, then once weekly for 6 weeks, and then monthly for 10 months. Seven to ten days following completion of one cycle of chemotherapy, patients undergo radiotherapy to the brain at a dose of 2.5 Gy daily for 5 days per week for approximately 4 weeks. Total dose to the whole brain and meninges is 30.0 Gy in 12 fractions, and total dose to the primary boost volume is 10.0 Gy in 4 fractions. During therapy, blood is drawn weekly and brain scans are performed every 3-12 weeks. An initial CSF sample will be obtained by lumbar puncture.

Eligibility criteria: Inclusion Criteria

Concurrent Medication: Required:

* PCP prophylaxis with Bactrim, dapsone, or aerosolized pentamidine.
* Oral candidiasis prophylaxis with fluconazole, ketoconazole, or clotrimazole oral troches.
* Antiretroviral agent available by therapy IND.
* MAI prophylaxis with rifabutin (in patients with CD4 counts \< 100 cells/mm3).

Patients must have:

* HIV infection.
* Primary CNS lymphoma with NO systemic involvement.

Prior Medication:

Allowed:

* Prior corticosteroids.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Concomitant malignancy other than Kaposi's sarcoma, curatively treated carcinoma in situ of the cervix, or squamous or basal cell carcinoma of the skin.
* Active uncontrolled infection.
* Renal failure, active nonmalignant duodenal ulcer, uncontrolled diabetes mellitus, or other serious medical conditions that would preclude aggressive cytotoxic chemotherapy administration.
* Active heart disease (congestive heart failure or heart block greater than first degree on EKG).

Concurrent Medication:

Excluded:

* Any investigational agent other than antiretroviral agents available by therapy IND.

Patients with the following prior conditions are excluded:

* No prior malignancy other than Kaposi's sarcoma, curatively treated carcinoma in situ of the cervix, or squamous cell or basal cell carcinoma of the skin.
* No new infectious complications within the past 2 weeks that require a change in antibiotics.
* History of myocardial infarction within the past 3 months.

Prior Medication:

Excluded:

* Prior chemotherapy other than for Kaposi's sarcoma.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco AIDS Clinic / San Francisco Gen Hosp
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Boston
country: United States
facility: Beth Israel Deaconess - West Campus
state: Massachusetts
city: Brookline
country: United States
facility: ECOG Data Management Office
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
Study officials:
name: Krigel RL
role: STUDY_CHAIR
name: Von Roenn J
role: STUDY_CHAIR
References:
citation: Schultz C, Scott C, Sherman W, Donahue B, Fields J, Murray K, Fisher B, Abrams R, Meis-Kindblom J. Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88-06. J Clin Oncol. 1996 Feb;14(2):556-64. doi: 10.1200/JCO.1996.14.2.556.