Clinical trial NCT00003993: Bryostatin 1 and Interleukin-2 in Treating Patients With Refractory Solid Tumors or Lymphoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage IV adult Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
small intestine lymphoma
unspecified adult solid tumor, protocol specific
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
primary central nervous system non-Hodgkin lymphoma
intraocular lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: National Institute on Aging - Baltimore
state: Maryland
Study officials:
affiliation: Gerontology Research Center
name: Igor Espinoza-Delgado, MD
role: STUDY_CHAIR
References: