Liposomal Doxorubicin Plus Combination Chemotherapy in Treating Patients With AIDS-Associated Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of liposomal doxorubicin plus combination chemotherapy in treating patients who have AIDS-associated non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: I. Determine the toxicity and maximum tolerated dose of doxorubicin HCl liposome when administered with combination chemotherapy in patients with AIDS-associated non-Hodgkin's lymphoma. II. Determine the optimal phase II dose of doxorubicin HCl liposome to be administered with the combination chemotherapy regimen. III. Determine the effect of this regimen on HIV viral load in these patients. IV. Determine the clinical response to this regimen by these patients. OUTLINE: This is a dose escalation study of doxorubicin HCl liposome. Patients are stratified by risk group (good vs poor). Patients receive doxorubicin HCl liposome IV, vincristine IV, and methotrexate intrathecally on day 1, followed by oral prednisone on days 1-5. Sargramostim (GM-CSF) is administered subcutaneously on days 5-14 until blood counts recover. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A minimum of 42-48 patients will be accrued for this study.

Official Title
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Phase I Trial of Liposomal Doxorubicin (Doxil) Based Combination Chemotherapy Regimen in AIDS-Associated Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: sargramostim
* Drug: methotrexate
* Drug: pegylated liposomal doxorubicin hydrochloride
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven good or poor prognosis AIDS-associated non-Hodgkin's lymphoma expressing CD20 antigen HIV positive Stage II-IV Good risk patients are defined as: Karnofsky 80-100% No prior history of AIDS defining illness No bone marrow involvement with lymphoma No clinical, radiographic, or cytologic evidence of CNS lymphoma Bidimensionally measurable disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 80-100% Life expectancy: At least 3 months Hematopoietic: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 75,000/mm3 Hemoglobin greater than 9 g/dL Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT less than 5 times ULN Alkaline phosphatase less than 5 times ULN Renal: Creatinine no greater than 1.5 times ULN Other: Not pregnant No active opportunistic or any other serious infection No other malignancy (including any other AIDS-associated malignancy) except stable cutaneous Kaposi's sarcoma No serious medical or psychiatric condition PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior doxorubicin or doxorubicin HCl liposome No prior chemotherapy for non-Hodgkin's lymphoma, except single dose of intrathecal chemotherapy at time of staging lumbar puncture Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: At least 2 weeks since major surgery Other: No concurrent treatment for Kaposi's sarcoma Concurrent antiretroviral therapy allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose group 1 - dose 1 of Doxorubicin HCL Liposome<br>Patients receive doxorubicin HCl liposome IV, vincristine IV, and methotrexate intrathecally on day 1, followed by oral prednisone on days 1-5. Sargramostim (GM-CSF) is administered subcutaneously on days 5-14 until blood counts recover. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter | Biological: sargramostim<br> <br> Drug: methotrexate<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> |
| Experimental: Dose group 2 - dose 2 of Doxorubicin HCL Liposome<br>Patients are stratified by risk group (good vs poor). Patients receive doxorubicin HCl liposome IV, vincristine IV, and methotrexate intrathecally on day 1, followed by oral prednisone on days 1-5. Sargramostim (GM-CSF) is administered subcutaneously on days 5-14 until blood counts recover. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter | Biological: sargramostim<br> <br> Drug: methotrexate<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> |
| Experimental: Dose Group 3 - dose 3 of Doxorubicin HCL Liposome<br>Patients are stratified by risk group (good vs poor). Patients receive doxorubicin HCl liposome IV, vincristine IV, and methotrexate intrathecally on day 1, followed by oral prednisone on days 1-5. Sargramostim (GM-CSF) is administered subcutaneously on days 5-14 until blood counts recover. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter | Biological: sargramostim<br> <br> Drug: methotrexate<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> |
| Experimental: Dose group 4 - dose 4 of Doxorubicin HCL Liposome<br>Patients are stratified by risk group (good vs poor). Patients receive doxorubicin HCl liposome IV, vincristine IV, and methotrexate intrathecally on day 1, followed by oral prednisone on days 1-5. Sargramostim (GM-CSF) is administered subcutaneously on days 5-14 until blood counts recover. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter | Biological: sargramostim<br> <br> Drug: methotrexate<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> |
| Experimental: Dose group 5 - dose 5 of Doxorubicin HCL Liposome<br>Patients are stratified by risk group (good vs poor). Patients receive doxorubicin HCl liposome IV, vincristine IV, and methotrexate intrathecally on day 1, followed by oral prednisone on days 1-5. Sargramostim (GM-CSF) is administered subcutaneously on days 5-14 until blood counts recover. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter | Biological: sargramostim<br> <br> Drug: methotrexate<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> |
| Experimental: Dose group 6 - dose 6 of Doxorubicin HCL Liposome<br>Patients are stratified by risk group (good vs poor). Patients receive doxorubicin HCl liposome IV, vincristine IV, and methotrexate intrathecally on day 1, followed by oral prednisone on days 1-5. Sargramostim (GM-CSF) is administered subcutaneously on days 5-14 until blood counts recover. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter | Biological: sargramostim<br> <br> Drug: methotrexate<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> |
| Experimental: Dose group 7 - dose 7 of Doxorubicin HCL Liposome<br>Patients are stratified by risk group (good vs poor). Patients receive doxorubicin HCl liposome IV, vincristine IV, and methotrexate intrathecally on day 1, followed by oral prednisone on days 1-5. Sargramostim (GM-CSF) is administered subcutaneously on days 5-14 until blood counts recover. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter | Biological: sargramostim<br> <br> Drug: methotrexate<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> |
| Experimental: MTD group<br>Patients are stratified by risk group (good vs poor). Patients receive doxorubicin HCl liposome IV, vincristine IV, and methotrexate intrathecally on day 1, followed by oral prednisone on days 1-5. Sargramostim (GM-CSF) is administered subcutaneously on days 5-14 until blood counts recover. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter | Biological: sargramostim<br> <br> Drug: methotrexate<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the toxicity and maximum tolerated dose of doxorubicin HCl liposome when administered with combination chemotherapy in patients with AIDS-associated non-Hodgkin's lymphoma. |  | baseline to last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the optimal phase II dose of doxorubicin HCl liposome to be administered with the combination chemotherapy regimen. |  | baseline to last dose of study drug | 
| Determine the effect of this regimen on HIV viral load in these patients |  | baseline to survival | 
| Determine the clinical response to this regimen by these patients |  | baseline to survival | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIDS-related diffuse large cell lymphoma, AIDS-related immunoblastic large cell lymphoma, AIDS-related small noncleaved cell lymphoma, AIDS-related diffuse mixed cell lymphoma, AIDS-related diffuse small cleaved cell lymphoma, AIDS-related lymphoblastic lymphoma