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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT01700673
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 25
• Location: 1
• Arms: 3
• Actual Duration (Months): 84
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Myelodysplastic Syndrome	Drug: Azacitidine; Biological: Sargramostim	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Jun 1, 2020
• Actual Study Completion Date: Jun 1, 2020

Arms and Interventions

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: Vidaza 5-azacytidine 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: Vidaza 5-azacytidine 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: Vidaza 5-azacytidine 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

Outcome Measures

Primary Outcome Measures

1. 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. We will report the percentage of participants with two year relapse-free survival.

Secondary Outcome Measures

1. 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

2. One-year RFS [1 year]

   We will report the number of participants with one year RFS

3. Overall Survival [2 years]

   Percentage of participants with overall survival at 2 years.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Study Chair: Margaret Showel, MD, JHU

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 27, 2016

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01700673
• Other Study ID Numbers: J1240; P01CA015396; NA_00072223
• First Posted: Oct 4, 2012
• Last Update Posted: Jun 16, 2022
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: maintenance treatment; stem cell transplant; cytarabine-based chemotherapy
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Azacitidine; Sargramostim

Study Results

Participant Flow

Arm/Group Title	Myeloablative BMT	Non-myeloablative BMT	Standard Consolidation
Arm/Group Description	Azacitidine and sargramostim after myeloablative stem cell transplant Azacitidine: Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles. Sargramostim: Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.	Azacitidine and sargramostim after non-myeloablative stem cell transplant Azacitidine: Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles. Sargramostim: Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.	Azacitidine and sargramostim after standard consolidation Azacitidine: Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles. Sargramostim: Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.
Period Title: Overall Study
STARTED	1	23	1
COMPLETED	1	17	1
NOT COMPLETED	0	6	0

Baseline Characteristics

Arm/Group Title	Myeloablative BMT	Non-myeloablative BMT	Standard Consolidation	Total
Arm/Group Description	Azacitidine and sargramostim after myeloablative stem cell transplant Azacitidine: Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles. Sargramostim: Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.	Azacitidine and sargramostim after non-myeloablative stem cell transplant Azacitidine: Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles. Sargramostim: Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.	Azacitidine and sargramostim after standard consolidation Azacitidine: Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles. Sargramostim: Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.	Total of all reporting groups
Overall Participants	1	23	1	25
Age, Customized (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 72 years	1 100%	23 100%	1 100%	25 100%
>=73 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	11 47.8%	1 100%	12 48%
Male	1 100%	12 52.2%	0 0%	13 52%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	2 8.7%	0 0%	2 8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 4.3%	0 0%	1 4%
White	1 100%	18 78.3%	1 100%	20 80%
More than one race	0 0%	1 4.3%	0 0%	1 4%
Unknown or Not Reported	0 0%	1 4.3%	0 0%	1 4%

Outcome Measures

1. Primary Outcome

Title	Two-year Relapse Free Survival of Patients
Description	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. We will report the percentage of participants with two year relapse-free survival.
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-myeloablative BMT	Myeloablative BMT	Standard Consolidation
Arm/Group Description	Azacitidine and sargramostim after non-myeloablative stem cell transplant	Azacitidine and sargramostim after myeloablative stem cell transplant	Azacitidine and sargramostim after standard consolidation
Measure Participants	17	1	1
Count of Participants [Participants]	8 800%	1 4.3%	1 100%

2. Secondary Outcome

Title	Hematologic Toxicity as Determined by Anemia
Description	Percentage of patients with anemia, the most commonly reported hematologic toxicity, after receiving the combination of Azacitidine and sargramostim
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-myeloablative BMT	Myeloablative BMT	Standard Consolidation
Arm/Group Description	Azacitidine and sargramostim after non-myeloablative stem cell transplant	Azacitidine and sargramostim after myeloablative stem cell transplant	Azacitidine and sargramostim after standard consolidation
Measure Participants	17	1	1
Count of Participants [Participants]	8 800%	1 4.3%	0 0%

3. Secondary Outcome

Title	One-year RFS
Description	We will report the number of participants with one year RFS
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-myeloablative BMT	Myeloablative BMT	Standard Consolidation
Arm/Group Description	Azacitidine and sargramostim after non-myeloablative stem cell transplant	Azacitidine and sargramostim after myeloablative stem cell transplant	Azacitidine and sargramostim after standard consolidation
Measure Participants	17	1	1
Count of Participants [Participants]	12 1200%	1 4.3%	1 100%

4. Secondary Outcome

Title	Overall Survival
Description	Percentage of participants with overall survival at 2 years.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-myeloablative	Myeloablative BMT	Standard Consolidation
Arm/Group Description	Azacitidine and sargramostim after non-myeloablative stem cell transplant	Azacitidine and sargramostim after myeloablative stem cell transplant	Azacitidine and sargramostim after standard consolidation
Measure Participants	11	1	1
Count of Participants [Participants]	6 600%	1 4.3%	1 100%

Adverse Events

Time Frame	2 years
Arm/Group Title	Non-myeloablative BMT		Myeloablative BMT		Standard Consolidation
Arm/Group Description	Azacitidine and sargramostim after non-myeloablative stem cell transplant		Azacitidine and sargramostim after myeloablative stem cell transplant		Azacitidine and sargramostim after standard consolidation
All Cause Mortality
	Non-myeloablative BMT		Myeloablative BMT		Standard Consolidation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/17 (47.1%)		0/1 (0%)		0/1 (0%)
Serious Adverse Events
	Non-myeloablative BMT		Myeloablative BMT		Standard Consolidation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/17 (23.5%)		0/1 (0%)		0/1 (0%)
Blood and lymphatic system disorders
anemia	2/17 (11.8%)		0/1 (0%)		0/1 (0%)
eosinophilia	1/17 (5.9%)		0/1 (0%)		0/1 (0%)
neutropenia	2/17 (11.8%)		0/1 (0%)		0/1 (0%)
leukopenia	2/17 (11.8%)		0/1 (0%)		0/1 (0%)
thrombocytopenia	1/17 (5.9%)		0/1 (0%)		0/1 (0%)
Infections and infestations
infections	4/17 (23.5%)		0/1 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Graft-vs-host disease	1/17 (5.9%)		0/1 (0%)		0/1 (0%)
rash	1/17 (5.9%)		0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Non-myeloablative BMT		Myeloablative BMT		Standard Consolidation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/17 (100%)		1/1 (100%)		1/1 (100%)
Blood and lymphatic system disorders
ALT increase	3/17 (17.6%)	12	0/1 (0%)	12	1/1 (100%)	12
anemia	8/17 (47.1%)	21	1/1 (100%)	21	0/1 (0%)	21
edema	2/17 (11.8%)	5	0/1 (0%)	5	1/1 (100%)	2
creatinine increase	2/17 (11.8%)	5	0/1 (0%)	5	0/1 (0%)	5
eosiniphilia	2/17 (11.8%)	3	0/1 (0%)	3	0/1 (0%)	3
neutropenia	5/17 (29.4%)	13	0/1 (0%)	13	1/1 (100%)	13
leukopenia	4/17 (23.5%)	12	0/1 (0%)	12	1/1 (100%)	12
thrombocytopenia	8/17 (47.1%)	23	0/1 (0%)	23	0/1 (0%)	23
Ear and labyrinth disorders
dizziness	4/17 (23.5%)	6	0/1 (0%)	6	1/1 (100%)	6
Gastrointestinal disorders
nausea	8/17 (47.1%)	13	1/1 (100%)	13	1/1 (100%)	2
anorexia	3/17 (17.6%)	6	0/1 (0%)	6	0/1 (0%)	6
constipation	4/17 (23.5%)	16	0/1 (0%)	16	1/1 (100%)	16
diarrhea	8/17 (47.1%)	15	0/1 (0%)	15	1/1 (100%)	15
dyspepsia	4/17 (23.5%)	4	0/1 (0%)	4	1/1 (100%)	4
General disorders
fatigue	9/17 (52.9%)	27	0/1 (0%)	27	1/1 (100%)	27
Infections and infestations
infections	14/17 (82.4%)	44	0/1 (0%)	44	1/1 (100%)	44
Musculoskeletal and connective tissue disorders
myalgia	4/17 (23.5%)	6	1/1 (100%)	6	0/1 (0%)	6
bone pain	7/17 (41.2%)	8	0/1 (0%)	8	1/1 (100%)	8
chills	2/17 (11.8%)	3	0/1 (0%)	3	0/1 (0%)	3
Nervous system disorders
headache	6/17 (35.3%)	8	0/1 (0%)	8	1/1 (100%)	8
insomnia	4/17 (23.5%)	9	0/1 (0%)	9	0/1 (0%)	9
Respiratory, thoracic and mediastinal disorders
cough	8/17 (47.1%)	14	0/1 (0%)	14	1/1 (100%)	14
dyspnea	4/17 (23.5%)	12	0/1 (0%)	12	0/1 (0%)	12
Skin and subcutaneous tissue disorders
injection site erythema	12/17 (70.6%)	17	1/1 (100%)	17	0/1 (0%)	17
graft-vs-host disease	4/17 (23.5%)	9	1/1 (100%)	9	0/1 (0%)	9
rash	8/17 (47.1%)	19	0/1 (0%)	19	1/1 (100%)	3
pruritis	6/17 (35.3%)	13	0/1 (0%)	13	1/1 (100%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.