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

NCT ID: NCT00003993

Last Updated: 2015-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-09-30

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.

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.

Conditions

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

Study Design

• Primary Study Purpose: TREATMENT

Interventions

aldesleukin

Intervention Type: BIOLOGICAL

bryostatin 1

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role: lead

Principal Investigators

Igor Espinoza-Delgado, MD

Role: STUDY_CHAIR

Gerontology Research Center

Locations

National Institute on Aging - Baltimore

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

NCI-T99-0015

Identifier Type: -

Identifier Source: secondary_id

LSUMC-9901

Identifier Type: -

Identifier Source: secondary_id

CDR0000067198

Identifier Type: -

Identifier Source: org_study_id