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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003993
• Other study ID #: CDR0000067198
• Secondary ID: NCI-T99-0015LSUM
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: April 28, 2015
• Start date: September 1999

Study information

• Verified date: May 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Small Intestine Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Biological:
• aldesleukin

Drug:
• bryostatin 1

Locations

Country	Name	City	State
United States	National Institute on Aging - Baltimore	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,