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

Sponsor

National Institute on Aging (NIA) (NIH)

Overall Status

Completed

CT.gov ID

NCT00003993

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific	Biological: aldesleukin Drug: bryostatin 1	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Primary Purpose:

Treatment

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

Study Start Date :

Sep 1, 1999

Actual Primary Completion Date :

Jul 1, 2008

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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