Bryostatin 1 and Interleukin-2 in Treating Patients With Refractory Solid Tumors or Lymphoma

April 28, 2015 updated by: National Institute on Aging (NIA)

A Phase lb Trial of the Combination of Bryostatin-1 and Low Dose Interleukin-2: Evaluation of the Functional and Molecular Status of Human Monocytes as Antigen Presenting Cells

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Combining chemotherapy and interleukin-2 may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-2 when given together with bryostatin 1 in treating patients with refractory solid tumors or lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the safety and side effects of bryostatin 1 and interleukin-2 in patients with refractory solid tumors or lymphomas.
  • Determine the maximum tolerated dose for interleukin-2 with bryostatin 1 in these patients.
  • Determine whether bryostatin 1 and interleukin-2 increase the expression of recognition and costimulatory molecules on human monocytes and their ability to act as antigen presenting cells.
  • Assess any anti-tumor response in these patients treated with this regimen.

OUTLINE: This is a dose escalation study of interleukin-2.

Patients receive bryostatin 1 IV over 24 hours on days 1 and 8, and interleukin-2 subcutaneously on days 1-5 and days 8-12. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of interleukin-2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study in less than 2 years.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • 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
    • Maryland
      • Baltimore, Maryland, United States, 21224-6825
        • National Institute on Aging - Baltimore

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:

  • Histologically proven solid tumor or lymphoma that is not curable by surgery, radiotherapy, or standard chemotherapy, or for which no curative therapy exists

  • Prostate cancer patients must have the following:

    • Tumor progression following blockade of both testicular and adrenal androgens
    • Serum testosterone in the castrate range (less than 20 ng/mL)
    • At least 3 months since prior suramin therapy
    • At least 4 weeks since prior flutamide or other antiandrogen medication and no evidence of response to treatment
    • Luprolide should continue if no prior orchiectomy
  • No prior or concurrent brain metastases

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0 or 1

Life expectancy:

  • At least 3 months

Hematopoietic:

  • WBC at least 3,500/mm^3 OR
  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 8 g/dL

Hepatic:

  • Hepatitis B surface antigen negative
  • PT no greater than 14 seconds
  • PTT no greater than 35 seconds
  • Bilirubin no greater than 1.5 mg/dL unless due to Gilbert's disease
  • SGOT and SGPT no greater than 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 2.5 times ULN
  • Albumin at least 2.5 g/dL

Renal:

  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance at least 50 mL/min
  • Corrected calcium at least 8.0 mg/dL, but no greater than 10.7 mg/dL

Cardiovascular:

  • No prior myocardial infarction, coronary artery disease (CAD), congestive heart failure, second or third degree AV block, or cardiac arrhythmias requiring treatment
  • No evidence of CAD on EKG

Pulmonary:

  • FEV1-1 at least 70% predicted
  • DLCO at least 60% predicted

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • At least 1 week since active infection requiring antibiotics
  • No other medical or psychiatric condition that would preclude study
  • No prior or concurrent seizure disorders controlled with medication

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior interleukin-2
  • At least 4 weeks since other prior biologic therapy for solid tumors or lymphomas

Chemotherapy:

  • See Disease Characteristics
  • At least 4 weeks since prior bryostatin 1
  • At least 4 weeks since other prior chemotherapy for solid tumors or lymphomas

Endocrine therapy:

  • See Disease Characteristics
  • At least 4 weeks since other prior endocrine therapy for solid tumors or lymphomas
  • No absolute requirement for corticosteroids

Radiotherapy:

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy for solid tumors or lymphomas

Surgery:

  • See Disease Characteristics
  • At least 4 weeks since prior surgery for solid tumors or lymphomas

Other:

  • No absolute requirement for nonsteroidal anti-inflammatory drugs or H2 blockers

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

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

September 1, 1999

Primary Completion (Actual)

July 1, 2008

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

April 29, 2015

Last Update Submitted That Met QC Criteria

April 28, 2015

Last Verified

May 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000067198
  • NCI-T99-0015
  • LSUMC-9901

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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