Trial Outcomes & Findings for MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia (NCT NCT00462605)

Results Overview

Response to treatment was assessed after two cycles, according to International Working Group (IWG) criteria. Cytogenetic responses were monitored in patients with abnormalities at baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2017-07-18

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I Patients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity. After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria. entinostat: Given PO sargramostim: Given SC
Overall Study STARTED	24
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I n=24 Participants Patients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity. After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria. entinostat: Given PO sargramostim: Given SC
Age, Continuous	71 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Region of Enrollment United States	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Response to treatment was assessed after two cycles, according to International Working Group (IWG) criteria. Cytogenetic responses were monitored in patients with abnormalities at baseline.

Outcome measures

Outcome measures
Measure	Arm I n=10 Participants Patients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity. After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria. entinostat: Given PO sargramostim: Given SC
Response (Complete and Partial Response) in Patients With Myeloid Disorders Complete Remission (CR)	0 Participants
Response (Complete and Partial Response) in Patients With Myeloid Disorders Partial Remission (PR)	1 Participants
Response (Complete and Partial Response) in Patients With Myeloid Disorders Hematologic Improvement in Neutrophils (HI-N)	2 Participants
Response (Complete and Partial Response) in Patients With Myeloid Disorders Stable Disease (SD)	5 Participants
Response (Complete and Partial Response) in Patients With Myeloid Disorders Progressive Disease (PD)	2 Participants

SECONDARY outcome

Timeframe: Baseline and after 2 cycles

Outcome measures

Outcome measures
Measure	Arm I n=10 Participants Patients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity. After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria. entinostat: Given PO sargramostim: Given SC
Clinical Activity Assessed by Change in Peripheral Blood Counts ANC +/- SEM at baseline	578 cell/mm^3 Standard Error 126
Clinical Activity Assessed by Change in Peripheral Blood Counts ANC +/- SEM after 2 cycles	1137 cell/mm^3 Standard Error 384

SECONDARY outcome

Timeframe: Baseline and after 2 cycles

Population: Due to the limited number of clinical responders, this outcome was not measured.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6, 12, 24, and 36 weeks

Population: Due to the limited number of clinical responders, the research assay was not done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 6, 12, 24, and 36 weeks

Population: Due to the limited number of clinical responders, the research assay was not done.

Outcome measures

Outcome data not reported

Adverse Events

Arm I

Serious events: 19 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I n=24 participants at risk Patients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity. After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria. entinostat: Given PO sargramostim: Given SC
Infections and infestations Neutropenic infection	20.8% 5/24
Musculoskeletal and connective tissue disorders Bone Pain	12.5% 3/24
General disorders Fatigue	8.3% 2/24
Cardiac disorders Pericardial effusion	4.2% 1/24
Musculoskeletal and connective tissue disorders Weakness	4.2% 1/24
Gastrointestinal disorders anorexia	4.2% 1/24
Respiratory, thoracic and mediastinal disorders hypoxia	8.3% 2/24
Nervous system disorders vasovagal episode	4.2% 1/24
Musculoskeletal and connective tissue disorders Joint pain	4.2% 1/24
Respiratory, thoracic and mediastinal disorders cough	4.2% 1/24
Respiratory, thoracic and mediastinal disorders pneumonitis	4.2% 1/24

Other adverse events

Other adverse events
Measure	Arm I n=24 participants at risk Patients receive oral MS-275 on days 1, 8, 15, and 22. Patients also receive sargramostim (GM-CSF) subcutaneously once daily on days 1-42 in courses 3 and 5 and on days 1-35 in courses 1, 2, 4, and 6. Treatment repeats every 6 weeks for 2-6 courses in the absence of disease progression or unacceptable toxicity. After completion of 2 courses of study therapy, patients who achieve a complete or partial response may receive an additional 4 courses. Patients who maintain stable disease for more than 2 months after completion of 6 courses of study therapy may receive an additional 6 courses at the time of disease progression, provided they meet original eligibility criteria. entinostat: Given PO sargramostim: Given SC
Metabolism and nutrition disorders hyponatremia	8.3% 2/24
Nervous system disorders confusion	8.3% 2/24
Infections and infestations Neutropenic infection	4.2% 1/24
Respiratory, thoracic and mediastinal disorders Dyspnea	4.2% 1/24
General disorders fatigue	4.2% 1/24
Musculoskeletal and connective tissue disorders back pain	4.2% 1/24
Metabolism and nutrition disorders hypocalcemia	4.2% 1/24
Gastrointestinal disorders GI bleed	4.2% 1/24
Musculoskeletal and connective tissue disorders Muscle weakness	8.3% 2/24

Additional Information

B. Douglas Smith

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phone: 410-614-5068

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60