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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: methotrexate; Drug: vincristine sulfate; Biological: sargramostim; Drug: pegylated liposomal doxorubicin hydrochloride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose group 1 - dose 1 of Doxorubicin HCL Liposome; 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	Drug: methotrexate; Drug: vincristine sulfate; Biological: sargramostim; Drug: pegylated liposomal doxorubicin hydrochloride
Experimental: Dose group 2 - dose 2 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	Drug: methotrexate; Drug: vincristine sulfate; Biological: sargramostim; Drug: pegylated liposomal doxorubicin hydrochloride
Experimental: Dose Group 3 - dose 3 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	Drug: methotrexate; Drug: vincristine sulfate; Biological: sargramostim; Drug: pegylated liposomal doxorubicin hydrochloride
Experimental: Dose group 4 - dose 4 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	Drug: methotrexate; Drug: vincristine sulfate; Biological: sargramostim; Drug: pegylated liposomal doxorubicin hydrochloride
Experimental: Dose group 5 - dose 5 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	Drug: methotrexate; Drug: vincristine sulfate; Biological: sargramostim; Drug: pegylated liposomal doxorubicin hydrochloride
Experimental: Dose group 6 - dose 6 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	Drug: methotrexate; Drug: vincristine sulfate; Biological: sargramostim; Drug: pegylated liposomal doxorubicin hydrochloride
Experimental: Dose group 7 - dose 7 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	Drug: methotrexate; Drug: vincristine sulfate; Biological: sargramostim; Drug: pegylated liposomal doxorubicin hydrochloride
Experimental: MTD group; 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	Drug: methotrexate; Drug: vincristine sulfate; Biological: sargramostim; Drug: pegylated liposomal doxorubicin hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Mansoor N. Saleh, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: June 1, 1997
• Primary Completion (Actual): January 1, 2001
• Study Completion (Actual): January 1, 2001

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: August 4, 2004
• First Posted (Estimate): August 5, 2004

Study Record Updates

• Last Update Posted (Estimate): April 12, 2013
• Last Update Submitted That Met QC Criteria: April 10, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: 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
• 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; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Sargramostim
• Other Study ID Numbers: CDR0000067402; UAB-9708; UAB-F970529007; NCI-G99-1627