Phase II Study of Azacitidine and Sargramostim as Maintenance Treatment for Poor-Risk AML or MDS

Johns Hopkins Medicine

Status and phase: Completed; Phase 2

Conditions: Myelodysplastic Syndrome; Acute Myeloid Leukemia

Treatments: Drug: Azacitidine; Biological: Sargramostim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01700673

NA_00072223 (Other Identifier)

J1240

P01CA015396 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

To determine the impact of maintenance therapy in patients with MDS/AML in remission.

Full description

We propose a phase II study to determine the impact of maintenance therapy with 5-azacytidine and GM-CSF in patients with poor-risk AML or MDS, who are in remission after definitive treatment with either stem cell transplant or cytarabine-based consolidation chemotherapy.

In order to precede relapse and to avoid lead time bias, treatment would need to commence within 185 days of definitive therapy. Furthermore, approximately 50% of relapses occur within the first year and up to 80% within two years after SCT, therefore we would limit the duration of maintenance therapy to one year, followed by two years of follow-up.

Enrollment: 25 patients

Sex: All

Ages: 6+ months old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age > 6 months
2. Initial diagnosis of poor -risk AML or MDS (defined in section 3.2), treated with either stem cell transplant or cytarabine-based consolidation chemotherapy, within the past 60-185 days
3. ECOG performance status 0-2
4. No morphologic evidence of leukemia or active MDS as determined by JHH Hematopathologist independent review of a bone marrow aspirate and biopsy done following the completion of therapy and within 14 days prior to enrollment
5. Peripheral blood count recovery: Neutrophil count ≥ 1000 /µL, platelet count ≥ 50x 109 /µL without platelet transfusions, and adequate hematocrit independent of red cell transfusions .
6. No evidence of extramedullary leukemia, such as CNS or soft tissue involvement
7. Adequate end organ function as measured by the following: AST and ALT < 4 x normal, total serum bilirubin < 2 x upper limit normal (unless due to hemolysis, Gilbert's syndrome, or ineffective erythropoiesis), creatinine < 2 x upper limit of normal
8. Ability to give informed consent
9. In agreement to use an effective barrier method of birth control to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile

Exclusion criteria

1. Patients with untreated or uncontrolled infections
2. Patients with untreated or uncontrolled grade 3 or 4 GVHD
3. Pregnancy and lactation
4. Concurrent use of any other investigational agents.
5. Known HIV-positive patients.
6. Known hypersensitivity to 5AC or GM-CSF

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 3 patient groups

Myeloablative BMT

Experimental group

Description:

Azacitidine and sargramostim after myeloablative stem cell transplant

Treatment:

Biological: Sargramostim

Drug: Azacitidine

Non-myeloablative BMT

Experimental group

Description:

Azacitidine and sargramostim after non-myeloablative stem cell transplant

Treatment:

Biological: Sargramostim

Drug: Azacitidine

Standard consolidation

Experimental group

Description:

Azacitidine and sargramostim after standard consolidation

Treatment:

Biological: Sargramostim

Drug: Azacitidine