Rituximab and Liposomal Doxorubicin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00244985

Enrollment

Registered

2005-10-27

Start date

2005-09-30

Completion date

2012-12-31

Last updated

2017-08-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

DRUGpegylated liposomal doxorubicin hydrochloride

BIOLOGICALrituximab

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 120 Years

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
Complete Response Rate at 20 Weeks	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

Measure	Time frame	Description
Progression Free Survival (PFS) Rate at 2 Years	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	2 years	Overall survival was defined as time from date of treatment initiation until date of death due to any cause.
Partial Response Rate at 20 Weeks	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	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Arm 1: Rituximab and Doxorubicin HCI Liposome Patients receive rituximab IV over 3-8 hours on day 1 and doxorubicin HCl liposome IV over 1-3 hours on day 3 rituximab: IV pegylated liposomal doxorubicin hydrochloride: IV	42
Total	42

Baseline characteristics

Characteristic	Arm 1: Rituximab and Doxorubicin HCI Liposome
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	18 Participants
Age, Categorical Between 18 and 65 years	24 Participants
Age, Continuous	62.3 years STANDARD_DEVIATION 11.2
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	39 Participants
Sex: Female, Male Female	19 Participants
Sex: Female, Male Male	23 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	42 / 42
serious Total, serious adverse events	6 / 42

Outcome results

Primary

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.

Time frame: 20 weeks