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

July 14, 2017 updated by: Roswell Park Cancer Institute

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Biological: rituximab
IV
Drug: pegylated liposomal doxorubicin hydrochloride
IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response Rate at 20 Weeks
Time Frame: 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.
20 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Collaborators

Ortho Biotech, Inc.

Investigators

  • Principal Investigator: Myron S. Czuczman, MD, Roswell Park Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

August 1, 2008

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

October 25, 2005

First Submitted That Met QC Criteria

October 25, 2005

First Posted (Estimate)

October 27, 2005

Study Record Updates

Last Update Posted (Actual)

August 17, 2017

Last Update Submitted That Met QC Criteria

July 14, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000447130
  • RPC 02-04 (Other Identifier: Roswell Park Cancer Institute)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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