Back to resultsRituximab and Liposomal Doxorubicin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Primary Purpose
Lymphoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rituximab
pegylated liposomal doxorubicin hydrochloride
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent small lymphocytic lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following indolent or aggressive B-cell non-Hodgkin's lymphoma (NHL) subtypes: Grade 1-3 follicular lymphoma Mantle cell lymphoma Small lymphocytic lymphoma Diffuse large B-cell lymphoma Diffuse mixed cell lymphoma Marginal zone lymphoma Relapsed or refractory CD20-positive disease Measurable disease Must have received ≥ 1 but < 4 prior standard chemotherapy regimens No Burkitt's lymphoma or precursor B-lymphoblastic lymphoma No CNS lymphoma PATIENT CHARACTERISTICS: Performance status Karnofsky 60-100% Life expectancy At least 6 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin > 7 g/dL Hepatic AST or ALT < 2 times upper limit of normal (unless due to primary disease) Bilirubin ≤ 2 mg/dL Renal Creatinine ≤ 2.0 mg/dL Cardiovascular LVEF ≥ 50% by MUGA and/or 2-D echocardiogram No history of New York Heart Association class II-IV cardiac disease No congestive heart failure Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known HIV positivity No uncontrolled active bacterial, viral, or fungal infection No other serious disease that would preclude study participation No other primary malignancy within the past 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy Recovered from prior immunotherapy Prior immunotherapy, including rituximab or other monoclonal antibody, allowed Chemotherapy See Disease Characteristics More than 4 weeks since prior chemotherapy and recovered No prior doxorubicin (or equivalent anthracycline) at a cumulative dose > 400 mg/m^2 No other concurrent chemotherapy Endocrine therapy Nonsteroidal hormones for nonlymphoma-related conditions (e.g., insulin for diabetes) allowed No concurrent corticosteroids except for a transient inflammatory reaction (i.e., skin rash or hives) Radiotherapy Recovered from prior radiotherapy No concurrent radiotherapy Surgery More than 4 weeks since prior major surgery (other than diagnostic surgery) and recovered Other No other concurrent antitumor agents No other concurrent investigational agents
Sites / Locations
- Roswell Park Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm 1: Rituximab and Doxorubicin HCI Liposome
Arm Description
Patients receive rituximab IV over 3-8 hours on day 1 and doxorubicin HCl liposome IV over 1-3 hours on day 3
Outcomes
Primary Outcome Measures
Complete Response Rate at 20 Weeks
Complete Response (CR): During observation no disease is apparent, including measurable and non-measurable disease, for at least 28 days, as confirmed by a second assessment following the original observation of no disease. All nodes visualized on imaging studies or palpable on exams must have regressed to normal size their greatest transverse diameter for nodes > 1.5 em before therapy). Previously involved nodes that were 1.1 to 1.5 in their greatest transverse diameter before treatment must have decreased to 1 cm in their greatest transverse diameter after treatment or by more than 75% in the sum of the products of the greatest diameters (SPD). The patient must also be free from symptoms related to lymphoma, if present before therapy with no worsening in performance status from baseline. Bone marrow, if initially positive at baseline, must be histologically negative for lymphoma and the liver and spleen, if enlarged due to lymphoma at baseline, should be normalized.
Secondary Outcome Measures
Partial Response Rate at 20 Weeks
Partial Response (PR): A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the > or = to 50% decrease. Additionally, no appearance of new lesions is noted.
Overall Response Rate (Complete and Partial Responses) at 20 Weeks
Complete Response (CR): During observation no disease is apparent, including measurable and non-measurable disease, for at least 28 days, as confirmed by a second assessment following the original observation of no disease. All nodes visualized on imaging studies or palpable on exams must have regressed to normal size their greatest transverse diameter for nodes > 1.5 before therapy. Partial Response (PR): A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the > or = to 50% decrease. Additionally, no appearance of new lesions is noted.
Progression Free Survival (PFS) Rate at 2 Years
Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions.
Overall Survival (OS) Rate at 2 Years
Overall survival was defined as time from date of treatment initiation until date of death due to any cause.
Full Information
NCT ID
NCT00244985
First Posted
October 25, 2005
Last Updated
July 14, 2017
Sponsor
Roswell Park Cancer Institute
Collaborators
Ortho Biotech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00244985
Brief Title
Rituximab and Liposomal Doxorubicin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title
A Phase I/II Pilot Study of the Safety and Efficacy of Rituxan (Chimeric Anti-CD20 Antibody) in Combination With Doxil (Liposomal Doxorubicin) Chemotherapy in Patients With Relapsing or Refractory Indolent or Aggressive B-Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
Ortho Biotech, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as liposomal doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with liposomal doxorubicin may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects of giving rituximab together with liposomal doxorubicin and to see how well they work in treating patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
Detailed Description
OBJECTIVES:
Primary
Determine the safety, including qualitative and quantitative toxic effects and their duration and reversibility, of rituximab and doxorubicin HCl liposome in patients with relapsed or refractory, indolent or aggressive CD20-positive B-cell non-Hodgkin's lymphoma.
Secondary
Determine the efficacy, including overall response rate and durability of objective response, of this regimen in these patients.
Correlate pretreatment functional, phenotypic, and genotypic characteristics of host immune effector cells with response in patients treated with this regimen.
OUTLINE: This is an open-label, pilot study.
Patients receive rituximab IV over 3-8 hours on day 1 and doxorubicin HCl liposome IV over 1-3 hours on day 3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 4 years.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent small lymphocytic lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: Rituximab and Doxorubicin HCI Liposome
Arm Type
Experimental
Arm Description
Patients receive rituximab IV over 3-8 hours on day 1 and doxorubicin HCl liposome IV over 1-3 hours on day 3
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
pegylated liposomal doxorubicin hydrochloride
Intervention Description
IV
Primary Outcome Measure Information:
Title
Complete Response Rate at 20 Weeks
Description
Complete Response (CR): During observation no disease is apparent, including measurable and non-measurable disease, for at least 28 days, as confirmed by a second assessment following the original observation of no disease. All nodes visualized on imaging studies or palpable on exams must have regressed to normal size their greatest transverse diameter for nodes > 1.5 em before therapy). Previously involved nodes that were 1.1 to 1.5 in their greatest transverse diameter before treatment must have decreased to 1 cm in their greatest transverse diameter after treatment or by more than 75% in the sum of the products of the greatest diameters (SPD). The patient must also be free from symptoms related to lymphoma, if present before therapy with no worsening in performance status from baseline. Bone marrow, if initially positive at baseline, must be histologically negative for lymphoma and the liver and spleen, if enlarged due to lymphoma at baseline, should be normalized.
Time Frame
20 weeks
Secondary Outcome Measure Information:
Title
Partial Response Rate at 20 Weeks
Description
Partial Response (PR): A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the > or = to 50% decrease. Additionally, no appearance of new lesions is noted.
Time Frame
20 weeks
Title
Overall Response Rate (Complete and Partial Responses) at 20 Weeks
Description
Complete Response (CR): During observation no disease is apparent, including measurable and non-measurable disease, for at least 28 days, as confirmed by a second assessment following the original observation of no disease. All nodes visualized on imaging studies or palpable on exams must have regressed to normal size their greatest transverse diameter for nodes > 1.5 before therapy. Partial Response (PR): A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the > or = to 50% decrease. Additionally, no appearance of new lesions is noted.
Time Frame
20 weeks
Title
Progression Free Survival (PFS) Rate at 2 Years
Description
Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions.
Time Frame
2 years
Title
Overall Survival (OS) Rate at 2 Years
Description
Overall survival was defined as time from date of treatment initiation until date of death due to any cause.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following indolent or aggressive B-cell non-Hodgkin's lymphoma (NHL) subtypes:
Grade 1-3 follicular lymphoma
Mantle cell lymphoma
Small lymphocytic lymphoma
Diffuse large B-cell lymphoma
Diffuse mixed cell lymphoma
Marginal zone lymphoma
Relapsed or refractory CD20-positive disease
Measurable disease
Must have received ≥ 1 but < 4 prior standard chemotherapy regimens
No Burkitt's lymphoma or precursor B-lymphoblastic lymphoma
No CNS lymphoma
PATIENT CHARACTERISTICS:
Performance status
Karnofsky 60-100%
Life expectancy
At least 6 months
Hematopoietic
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 75,000/mm^3
Hemoglobin > 7 g/dL
Hepatic
AST or ALT < 2 times upper limit of normal (unless due to primary disease)
Bilirubin ≤ 2 mg/dL
Renal
Creatinine ≤ 2.0 mg/dL
Cardiovascular
LVEF ≥ 50% by MUGA and/or 2-D echocardiogram
No history of New York Heart Association class II-IV cardiac disease
No congestive heart failure
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No known HIV positivity
No uncontrolled active bacterial, viral, or fungal infection
No other serious disease that would preclude study participation
No other primary malignancy within the past 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
Biologic therapy
Recovered from prior immunotherapy
Prior immunotherapy, including rituximab or other monoclonal antibody, allowed
Chemotherapy
See Disease Characteristics
More than 4 weeks since prior chemotherapy and recovered
No prior doxorubicin (or equivalent anthracycline) at a cumulative dose > 400 mg/m^2
No other concurrent chemotherapy
Endocrine therapy
Nonsteroidal hormones for nonlymphoma-related conditions (e.g., insulin for diabetes) allowed
No concurrent corticosteroids except for a transient inflammatory reaction (i.e., skin rash or hives)
Radiotherapy
Recovered from prior radiotherapy
No concurrent radiotherapy
Surgery
More than 4 weeks since prior major surgery (other than diagnostic surgery) and recovered
Other
No other concurrent antitumor agents
No other concurrent investigational agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Myron S. Czuczman, MD
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Rituximab and Liposomal Doxorubicin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
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