Bryostatin 1 and Rituximab in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

April 29, 2015 updated by: National Institute on Aging (NIA)

A Phase II Trial Of Bryostatin-1 In Combination With Rituximab In Rituximab-Refractory Indolent B-cell Non Hodgkin's Lymphoma And Chronic Lymphocytic Leukemia

RATIONALE: Drugs used in chemotherapy, such as bryostatin 1, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Bryostatin 1 may help rituximab kill more cancer cells by making them more sensitive to the drug.

PURPOSE: This phase II trial is studying how well giving bryostatin 1 together with rituximab works in treating patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia that has not responded to previous treatment with rituximab.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the feasibility and safety of bryostatin 1 and rituximab in patients with rituximab-refractory indolent B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia (CLL).
  • Determine the antitumor response in patients treated with this regimen.

Secondary

  • Determine the effects of this regimen on the functional and molecular status of effector cells (i.e., NK cells, monocytes, and dendritic cells) in these patients.
  • Determine the expression of CD20 and complement-inhibitory molecules on tumor cells before and after treatment with this regimen in these patients.
  • Determine the effects of this regimen on the global gene expression pattern in CLL cells of these patients.

OUTLINE: This is a multicenter study.

Patients receive bryostatin 1 IV continuously over 24 hours on days -6, 2, and 9 of course 1 and on days 2 and 9 of courses 2-6. Patients also receive rituximab IV over 4 hours on days 1, 8, 15, and 22 of courses 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: Approximately 18-48 patients (9-24 with non-Hodgkin's lymphoma and 9-24 with chronic lymphocytic leukemia) will be accrued for this study within 12-30 months.

Study Type

Interventional

Enrollment (Anticipated)

48

Phase

  • Phase 2

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
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • NIH - Warren Grant Magnuson Clinical Center

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • One of the following histologically or cytologically confirmed diseases:

    • Indolent B-cell non-Hodgkin's lymphoma (NHL)

      • Stage II-IV disease

    • Chronic lymphocytic leukemia (CLL) meeting 1 of the following risk criteria:

      • Intermediate-risk with progressive disease
      • High-risk, modified Rai stage disease
  • CD20-positive by flow cytometry or immunohistochemistry
  • Measurable disease
  • Rituximab-refractory disease, defined as failure to achieve a response to the last course of prior treatment with rituximab alone or in combination with other therapeutic modalities
  • No known neoplastic leptomeningeal involvement and/or brain metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 3 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 50,000/mm^3
  • WBC ≥ 3,000/mm^3

Hepatic

  • AST and ALT ≤ 2.5 times upper limit of normal
  • Bilirubin normal (unless due to Gilbert's disease or organ involvement by NHL or CLL)

Renal

  • Creatinine normal OR
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative

  • No history of anaphylaxis or immunoglobulin (Ig) E-mediated hypersensitivity to murine protein

    • Prior infusion reactions to rituximab without an IgE component allowed
  • No active or ongoing infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • See Radiotherapy
  • At least 12 weeks since prior rituximab
  • More than 4 weeks since prior immunotherapy and recovered

Chemotherapy

  • No more than 3 prior chemotherapy regimens
  • More than 4 weeks since prior chemotherapy and recovered

Endocrine therapy

  • No concurrent glucocorticoids

Radiotherapy

  • At least 12 weeks since prior radioimmunotherapy
  • More than 4 weeks since prior radiotherapy and recovered

Surgery

  • Not specified

Other

  • At least 4 weeks since prior therapy for the malignancy
  • No other concurrent anticancer therapy
  • 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
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Antitumor response
Feasability and safety

Secondary Outcome Measures

Outcome Measure
Functional and molecular status of effector cells
Expression of CD20 and complement-inhibitory molecules on tumor cells before and after treatment
Effects on global gene expression pattern in chronic lymphocytic leukemia cells

Collaborators and Investigators

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

Sponsor

National Institute on Aging (NIA)

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Igor Espinoza-Delgado, MD, Gerontology Research Center

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

July 1, 2004

Primary Completion (Actual)

October 1, 2007

Study Registration Dates

First Submitted

July 8, 2004

First Submitted That Met QC Criteria

July 9, 2004

First Posted (Estimate)

July 12, 2004

Study Record Updates

Last Update Posted (Estimate)

April 30, 2015

Last Update Submitted That Met QC Criteria

April 29, 2015

Last Verified

January 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000377250
  • NIA-CII0301
  • NCI-6216

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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