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

Phase 2

Completed

• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome
• Interventions: Drug: Azacitidine; Biological: Sargramostim

• Registration Number: NCT01700673
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

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

Detailed 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.

Study Timeline

• Study First Submitted: 2012-10-02
• Study First Submitted QC: 2012-10-03
• Study First Posted: 2012-10-04
• Study Start: 2013-06
• Primary Completion: 2020-06
• Study Completion: 2020-06
• Status Verified: 2021-08
• Results First Submitted: 2021-08-06
• Results First Submitted QC: 2021-08-06
• Results First Posted: 2021-09-02
• Last Update Submitted: 2022-09-23
• Last Update Posted: 2022-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Myeloablative BMT	Azacitidine	Azacitidine and sargramostim after myeloablative stem cell transplant
Myeloablative BMT	Sargramostim	Azacitidine and sargramostim after myeloablative stem cell transplant
Non-myeloablative BMT	Azacitidine	Azacitidine and sargramostim after non-myeloablative stem cell transplant
Non-myeloablative BMT	Sargramostim	Azacitidine and sargramostim after non-myeloablative stem cell transplant
Standard consolidation	Azacitidine	Azacitidine and sargramostim after standard consolidation
Standard consolidation	Sargramostim	Azacitidine and sargramostim after standard consolidation

Primary Outcome Measures

Name	Time	Method
Two-year Relapse Free Survival of Patients	2 year	To evaluate the two-year relapse-free survival (RFS) of patients with poor-risk Acute Myeloid Leukemia (AML) or Myelodysplasia (MDS), who receive maintenance treatment with 5-Azacytidine (5AC) in combination with sargramostim (GM-CSF) during remission, following definitive therapy with either a stem cell transplant (SCT) or cytarabine-based consolidation chemotherapy.

Secondary Outcome Measures

Name	Time	Method
Hematologic Toxicity as Determined by Anemia	1 year	Percentage of patients with anemia, the most commonly reported hematologic toxicity, after receiving the combination of Azacitidine and sargramostim
One-year RFS	1 year	We will report the number of participants with one year RFS
Overall Survival	2 years	Percentage of participants with overall survival at 2 years.

Trial Locations

Locations (1)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States