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

Tracking Information
First Submitted Date ICMJE	December 10, 1999
First Posted Date ICMJE	August 5, 2004
Last Update Posted Date	April 12, 2013
Study Start Date ICMJE	June 1997
Actual Primary Completion Date	January 2001 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 10, 2013)	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. [ Time Frame: baseline to last dose of study drug ]
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00004162 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 10, 2013)	Determine the optimal phase II dose of doxorubicin HCl liposome to be administered with the combination chemotherapy regimen. [ Time Frame: baseline to last dose of study drug ]; Determine the effect of this regimen on HIV viral load in these patients [ Time Frame: baseline to survival ]; Determine the clinical response to this regimen by these patients [ Time Frame: baseline to survival ]
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Liposomal Doxorubicin Plus Combination Chemotherapy in Treating Patients With AIDS-Associated Non-Hodgkin's Lymphoma
Official Title ICMJE	Phase I Trial of Liposomal Doxorubicin (Doxil) Based Combination Chemotherapy Regimen in AIDS-Associated Non-Hodgkin's Lymphoma
Brief Summary	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	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 ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Lymphoma
Intervention ICMJE	Biological: sargramostim; Drug: methotrexate; Drug: pegylated liposomal doxorubicin hydrochloride; Drug: vincristine sulfate
Study Arms	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 Interventions: Biological: sargramostim Drug: methotrexate Drug: pegylated liposomal doxorubicin hydrochloride Drug: vincristine sulfate; 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 Interventions: Biological: sargramostim Drug: methotrexate Drug: pegylated liposomal doxorubicin hydrochloride Drug: vincristine sulfate; 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 Interventions: Biological: sargramostim Drug: methotrexate Drug: pegylated liposomal doxorubicin hydrochloride Drug: vincristine sulfate; 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 Interventions: Biological: sargramostim Drug: methotrexate Drug: pegylated liposomal doxorubicin hydrochloride Drug: vincristine sulfate; 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 Interventions: Biological: sargramostim Drug: methotrexate Drug: pegylated liposomal doxorubicin hydrochloride Drug: vincristine sulfate; 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 Interventions: Biological: sargramostim Drug: methotrexate Drug: pegylated liposomal doxorubicin hydrochloride Drug: vincristine sulfate; 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 Interventions: Biological: sargramostim Drug: methotrexate Drug: pegylated liposomal doxorubicin hydrochloride Drug: vincristine sulfate; 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 Interventions: Biological: sargramostim Drug: methotrexate Drug: pegylated liposomal doxorubicin hydrochloride Drug: vincristine sulfate
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Estimated Enrollment ICMJE; (submitted: April 10, 2013)	48
Original Enrollment ICMJE	Not Provided
Actual Study Completion Date	January 2001
Actual Primary Completion Date	January 2001 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00004162
Other Study ID Numbers ICMJE	CDR0000067402; UAB-9708; UAB-F970529007; NCI-G99-1627
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	University of Alabama at Birmingham
Study Sponsor ICMJE	University of Alabama at Birmingham
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Study Chair: Mansoor N. Saleh, MD University of Alabama at Birmingham
PRS Account	University of Alabama at Birmingham
Verification Date	April 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP