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

A Phase II Study of 5-Azacitidine (5AC) in Combination With Sargramostim (GM-CSF) as Maintenance Treatment, After Definitive Therapy With Either Stem Cell Transplant (SCT) or Cytarabine-based Chemotherapy, in Patients With Poor-risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

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

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Azacitidine; Biological: Sargramostim

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 Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Myeloablative BMT; Azacitidine and sargramostim after myeloablative stem cell transplant	Drug: Azacitidine; Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Names: Azacytidine; Vidaza; 5-azacytidine; Biological: Sargramostim; Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Names: GM-CSF
Experimental: Non-myeloablative BMT; Azacitidine and sargramostim after non-myeloablative stem cell transplant	Drug: Azacitidine; Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Names: Azacytidine; Vidaza; 5-azacytidine; Biological: Sargramostim; Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Names: GM-CSF
Experimental: Standard consolidation; Azacitidine and sargramostim after standard consolidation	Drug: Azacitidine; Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Names: Azacytidine; Vidaza; 5-azacytidine; Biological: Sargramostim; Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Names: GM-CSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Two-year Relapse Free Survival of Patients	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.	2 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Margaret Showel, MD, JHU

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2013
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: October 2, 2012
• First Submitted That Met QC Criteria: October 3, 2012
• First Posted (Estimate): October 4, 2012

Study Record Updates

• Last Update Posted (Actual): October 18, 2022
• Last Update Submitted That Met QC Criteria: September 23, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: stem cell transplant; maintenance treatment; cytarabine-based chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Azacitidine; Sargramostim
• Other Study ID Numbers: J1240; P01CA015396 (U.S. NIH Grant/Contract); NA_00072223 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO