Acute Myelogenous Leukemia, Myelodysplastic Syndrome
Conditions
Keywords
AML, acute myelogenous leukemia, MDS, myelodysplastic syndrome, bryostatin 1, all-trans retinoic acid, ATRA
Brief summary
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
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.
Interventions
DRUGAll-trans retinoic acid
DRUGBryostatin 1
Sponsors
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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. | — |
Countries
United States
Outcome results
None listed