Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of bryostatin 1 combined with sargramostim in treating patients who have refractory myeloid cancer.

Further Study Information

OBJECTIVES:

• Determine the maximum tolerated dose of bryostatin 1 when administered with sargramostim (GM-CSF) in patients with refractory myeloid malignancies.

• Determine the toxicity frequency of this regimen in these patients.

• Determine the pharmacokinetics of bryostatin 1 in these patients.

OUTLINE: This is a dose-escalation study of bryostatin 1.

Patients receive bryostatin 1 IV continuously and sargramostim (GM-CSF) subcutaneously once daily on days 1-21. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with disease stabilization or improvement may continue treatment for up to 12 courses.

Cohorts of 2 patients receive escalating doses of bryostatin 1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 30% of patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study within 12-18 months.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Myelodysplastic syndromes (MDS) by bone marrow aspiration and/or biopsy indicating primary refractory leukopenia or thrombocytopenia with morphologic features of MDS

• Refractory anemia (RA) and RA with ringed sideroblasts allowed provided transfusion dependent

• No RA with 5q syndrome

• Chronic myelomonocytic leukemia allowed

• Failure to achieve remission after intensive chemotherapy allowed if received chemotherapy more than 1 month prior to study

• Progression on other prior institutional trials including phenylbutyrate, tretinoin, or azacitidine allowed

• Relapsed acute myeloid leukemia (AML) by bone marrow aspiration or biopsy

• No acute promyelocytic leukemia

• WBC less than 30,000/mm^3 and stable for at least 7 days

• Unlikely to require cytotoxic therapy during study

• Newly diagnosed AML

• Previously untreated

• Not a candidate for potentially curative intensive chemotherapy

• Refused prior chemotherapy or deemed poor medical candidate for AML induction chemotherapy

• Accelerated or blastic phase chronic myelogenous leukemia (CML)

• Previously treated chronic phase CML allowed

• At least 2 weeks since prior treatment for accelerated or blastic phase CML

• Blast count less than 30,000/mm^3 and stable for at least 7 days

• No lymphoid blast phase CML

• Symptomatic paroxysmal nocturnal hemoglobinuria (PNH) associated with disease

• Life-threatening complications of illness (e.g., abdominal, central vein or cerebral thromboses, active infections, or recurrent symptomatic hemolytic crises) with no other treatment options allowed

• Not a candidate for potentially curative bone marrow transplantation

• Stable bone marrow function for more than 10 days prior to study (no WBC doubling within this time period)

• No active CNS disease

• Negative cytology by lumbar puncture for suspected CNS disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 2 months

Hematopoietic:

• See Disease Characteristics

• Hemoglobin at least 8 g/dL (transfusion allowed)

Hepatic:

• Bilirubin less than 1.6 mg/dL (unless secondary to hemolysis)

• SGOT/SGPT less than 2 times upper limit of normal unless disease related (e.g., PNH or extramedullary disease)

Renal:

• Creatinine less than 2.0 mg/dL

Cardiovascular:

• No disseminated intravascular coagulation

Pulmonary:

• No evidence of pulmonary leukostasis

Other:

• No radiographic evidence of active infection

• No untreated positive blood cultures

• No intolerance to sargramostim (GM-CSF)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

• At least 2 weeks since prior hematopoietic growth factors for myeloid disorder

• At least 2 weeks since prior biologic therapy (e.g., monoclonal antibodies) for myeloid disorder

• Recovered from prior biologic therapy

Chemotherapy:

• See Disease Characteristics

• At least 2 weeks since prior chemotherapy (except hydroxyurea for WBC greater than 10,000/mm^3) for myeloid disorder and recovered

• No prior bryostatin 1

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Trial Contact Information

Trial Lead Organizations/Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

B. Douglas Smith

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00012376
Information obtained from ClinicalTrials.gov on December 14, 2011

Back to Top