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

Alternate Title

Chemotherapy Plus Sargramostim in Treating Patients With Refractory Myeloid Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	JHOC-J0051 NCI-951, NCT00012376, 951

Objectives

1. Determine the maximum tolerated dose of bryostatin 1 when administered with sargramostim (GM-CSF) in patients with refractory myeloid malignancies.
2. Determine the toxicity frequency of this regimen in these patients.
3. Determine the pharmacokinetics of bryostatin 1 in these patients.

Entry 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/mm³ 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/mm³ 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

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/mm³) for myeloid disorder and recovered
• No prior bryostatin 1

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

B. Douglas Smith, MD, Protocol chair		Ph: 410-614-5068 Email: smithdo@jhmi.edu

Registry Information
Official Title		Dose Finding Study of Bryostatin-1 and GM-CSF in Refractory Myeloid Malignancies
Trial Start Date		2001-03-05
Registered in ClinicalTrials.gov		NCT00012376
Date Submitted to PDQ		2001-02-05
Information Last Verified		2005-05-10
NCI Grant/Contract Number		P01-CA15396

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