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Entinostat And Imatinib Mesylate In Treating Patients With Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT01383447
Recruitment Status : Terminated (This study was halted prematurely by the NCI for low accrual.)
First Posted : June 28, 2011
Results First Posted : August 8, 2017
Last Update Posted : August 8, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Interventions Drug: entinostat
Drug: imatinib mesylate
Other: laboratory biomarker analysis
Other: pharmacological study
Genetic: western blotting
Other: immunohistochemistry staining method
Other: flow cytometry
Genetic: polymerase chain reaction
Other: high performance liquid chromatography
Other: mass spectrometry
Enrollment 2

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Entinostat and Imatinib Mesylate)
Hide Arm/Group Description

Patients receive entinostat PO daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

entinostat: Given PO

imatinib mesylate: Given PO

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

western blotting: Correlative studies

immunohistochemistry staining method: Correlative studies

flow cytometry: Correlative studies

polymerase chain reaction: Correlative studies

high performance liquid chromatography: Correlative studies

mass spectrometry: Correlative studies

Period Title: Overall Study
Started 2
Completed 0
Not Completed 2
Arm/Group Title Treatment (Entinostat and Imatinib Mesylate)
Hide Arm/Group Description

Patients receive entinostat PO daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

entinostat: Given PO

imatinib mesylate: Given PO

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

western blotting: Correlative studies

immunohistochemistry staining method: Correlative studies

flow cytometry: Correlative studies

polymerase chain reaction: Correlative studies

high performance liquid chromatography: Correlative studies

mass spectrometry: Correlative studies

Overall Number of Baseline Participants 2
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
<=18 years
0
   0.0%
Between 18 and 65 years
1
  50.0%
>=65 years
1
  50.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
Female
1
  50.0%
Male
1
  50.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
2
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants
2
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of Entinostat When Given in Combination With Imatinib Mesylate
Hide Description The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Time Frame Up to 30 days post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This study was halted prematurely by the NCI for low accrual. No results were analyzed.
Arm/Group Title Treatment (Entinostat and Imatinib Mesylate)
Hide Arm/Group Description:

Patients receive entinostat PO daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

entinostat: Given PO

imatinib mesylate: Given PO

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

western blotting: Correlative studies

immunohistochemistry staining method: Correlative studies

flow cytometry: Correlative studies

polymerase chain reaction: Correlative studies

high performance liquid chromatography: Correlative studies

mass spectrometry: Correlative studies

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Rate of Complete Response (CR) for Adults With Relapsed/Refractory Ph+ ALL Treated With a Combination of Entinostat (at the Dose Determined in Phase 1) and Imatinib Mesylate
Hide Description [Not Specified]
Time Frame Up to 30 days post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This study was halted prematurely by the NCI for low accrual. No results were analyzed.
Arm/Group Title Treatment (Entinostat and Imatinib Mesylate)
Hide Arm/Group Description:

Patients receive entinostat PO daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

entinostat: Given PO

imatinib mesylate: Given PO

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

western blotting: Correlative studies

immunohistochemistry staining method: Correlative studies

flow cytometry: Correlative studies

polymerase chain reaction: Correlative studies

high performance liquid chromatography: Correlative studies

mass spectrometry: Correlative studies

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Progression Free Survival (PFS) for Adults With Relapsed/Refractory Ph+ ALL Treated With Combination of Entinostat and Imatinib Mesylate
Hide Description The Kaplan-Meier estimator will be used to estimate PFS with a 95% confidence interval from study entry.
Time Frame At 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This study was halted prematurely by the NCI for low accrual. No results were analyzed.
Arm/Group Title Treatment (Entinostat and Imatinib Mesylate)
Hide Arm/Group Description:

Patients receive entinostat PO daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

entinostat: Given PO

imatinib mesylate: Given PO

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

western blotting: Correlative studies

immunohistochemistry staining method: Correlative studies

flow cytometry: Correlative studies

polymerase chain reaction: Correlative studies

high performance liquid chromatography: Correlative studies

mass spectrometry: Correlative studies

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Comparative Pharmacokinetics (PK) and Pharmacodynamics (PD) of Entinostat Alone vs. Entinostat Plus Imatinib Mesylate
Hide Description Entinostat concentrations will be compared when administered alone or in combination with imatinib by paired Student’s t test (day 4 vs 11 concentrations) or Wilcoxon signed rank tests as appropriate. Association between exposure parameters and PD endpoints (e.g., apoptosis, histone acetylation, BCR-ABL expression) will be assessed using Fisher’s exact tests or Wilcoxon rank sum tests as appropriate.
Time Frame Day 4 and 11
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This study was halted prematurely by the NCI for low accrual. No results were analyzed.
Arm/Group Title Treatment (Entinostat and Imatinib Mesylate)
Hide Arm/Group Description:

Patients receive entinostat PO daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

entinostat: Given PO

imatinib mesylate: Given PO

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

western blotting: Correlative studies

immunohistochemistry staining method: Correlative studies

flow cytometry: Correlative studies

polymerase chain reaction: Correlative studies

high performance liquid chromatography: Correlative studies

mass spectrometry: Correlative studies

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Predictive Values of Levels of Flow Cytometric Minimal Residual Disease (MRD) on Duration of Progression Free Survival for the Study Population
Hide Description Kaplan-Meier PFS curves and cumulative incidence of progression curves will be generated for patients above vs. below each threshold, and log rank will be used to compare the curves.
Time Frame Day 29
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This study was halted prematurely by the NCI for low accrual. No results were analyzed.
Arm/Group Title Treatment (Entinostat and Imatinib Mesylate)
Hide Arm/Group Description:

Patients receive entinostat PO daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

entinostat: Given PO

imatinib mesylate: Given PO

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

western blotting: Correlative studies

immunohistochemistry staining method: Correlative studies

flow cytometry: Correlative studies

polymerase chain reaction: Correlative studies

high performance liquid chromatography: Correlative studies

mass spectrometry: Correlative studies

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Entinostat and Imatinib Mesylate)
Hide Arm/Group Description

Patients receive entinostat PO daily on days 1, 8, 15, and 22 and imatinib mesylate PO twice daily on days 1-28 (days 4-28 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

entinostat: Given PO

imatinib mesylate: Given PO

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

western blotting: Correlative studies

immunohistochemistry staining method: Correlative studies

flow cytometry: Correlative studies

polymerase chain reaction: Correlative studies

high performance liquid chromatography: Correlative studies

mass spectrometry: Correlative studies

All-Cause Mortality
Treatment (Entinostat and Imatinib Mesylate)
Affected / at Risk (%)
Total   0/2 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Entinostat and Imatinib Mesylate)
Affected / at Risk (%)
Total   0/2 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Entinostat and Imatinib Mesylate)
Affected / at Risk (%)
Total   1/2 (50.00%) 
Gastrointestinal disorders   
nausea   1/2 (50.00%) 
General disorders   
Edema: lower limb   1/2 (50.00%) 
Fatigue   1/2 (50.00%) 
Metabolism and nutrition disorders   
Hypophosphatemia   1/2 (50.00%) 
Musculoskeletal and connective tissue disorders   
Pain: bone marrow site   1/2 (50.00%) 
Psychiatric disorders   
Insomnia   1/2 (50.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Results Point of Contact
Name/Title: Dr. Patrick Brown
Organization: Johns Hopkins Sidney Kimmel Cancer Center
Phone: 410-614-4915
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01383447     History of Changes
Other Study ID Numbers: NCI-2010-02202
J1023
U01CA070095 ( U.S. NIH Grant/Contract )
First Submitted: May 5, 2011
First Posted: June 28, 2011
Results First Submitted: April 14, 2017
Results First Posted: August 8, 2017
Last Update Posted: August 8, 2017