Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	NCI-T99-0015 LSUMC-9901, NCT00003993

Objectives

1. Determine the safety and side effects of bryostatin 1 and interleukin-2 in patients with refractory solid tumors or lymphomas.
2. Determine the maximum tolerated dose for interleukin-2 with bryostatin 1 in these patients.
3. 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.
4. Assess any anti-tumor response in these patients treated with this regimen.

Entry 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

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0 or 1

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,500/mm³

  OR

• Granulocyte count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

National Institute on Aging

Igor Espinoza-Delgado, MD, Protocol chair		Ph: 410-558-8190 Email: espinozaig@grc.nia.nih.gov

Registry Information
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
Trial Start Date		1999-09-07
Trial Completion Date		2008-07-31
Registered in ClinicalTrials.gov		NCT00003993
Date Submitted to PDQ		1999-07-07
Information Last Verified		2006-05-02
NCI Grant/Contract Number		CA83632

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