A Study of All-Trans Retinoic Acid (ATRA) and Bryostatin in Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects of the combination of all-trans retinoic acid in combination with one of two schedules of Bryostatin 1 in patients with myelodysplasia and acute myelogenous leukemia.

Detailed Description
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All patients receive all-trans retinoic acid at a dose of 150 mg/m2/day and patients are randomized to one of two schedules of Bryostatin 1. Arm 1: Bryostatin 1 is administered at a dose of 60 mcg/m2 as a 30 minute intravenous (IV) infusion on days 8 and 22. Arm 2: Bryostatin 1 is administered at a dose of 40 mcg/m2 as a 72 hour IV infusion starting on days 8 and 22. Patients are assessed for response on day +50 with a bone marrow examination and patients with either a clinical response or stable disease receive further therapy. Bryostatin 1 pharmacokinetic samples are to be drawn on days 1, 8 and 50 of each cycle.

Official Title
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A Randomized Phase II Trial of All-Trans Retinoic Acid and One of Two Schedules of Bryostatin 1 in Patients With Refractory Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Conditions
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Acute Myelogenous Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: All-trans retinoic acid
* Drug: Bryostatin 1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with AML who have failed induction chemotherapy. Patients with secondary AML Patients with AML over age 60 who are deemed not to be a candidate for chemotherapy. Patients with any subtype of MDS. Age 18 or greater. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Satisfactory liver and kidney function. Greater than 4 weeks from prior chemotherapy or radiation therapy. Exclusion Criteria: Central nervous system abnormality. Uncontrolled active infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: All-trans retinoic acid|nan|
|Drug: Bryostatin 1|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This study is designed to test the therapeutic effect of combining Bryostatin 1 with the known maximum tolerated dose of all-trans retinoic acid in patients with either MDS or AML. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This study will also determine the ability of Bryostatin 1 in combination with ATRA in humans to induce differentiation of human leukemic cells and to cause changes in the levels of protein kinase C isoenzymes in these cells. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, acute myelogenous leukemia, MDS, myelodysplastic syndrome, bryostatin 1, all-trans retinoic acid, ATRA