Back to resultsStudy to Determine Safety, Pharmacokinetics and Efficacy of GMI-1271 in Combination With Chemotherapy in AML
Primary Purpose
Leukemia, Myeloid, Acute
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GMI-1271
Mitoxantrone
Etoposide
Cytarabine
Idarubicin
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring AML, Acute myeloid leukemia, E-selectin, relapse refractory, elderly newly diagnosed, induction
Eligibility Criteria
Inclusion criteria:
- AML (including secondary AML) diagnosed as per WHO criteria
For relapsed/refractory subjects only:
- Subjects age ≥ 18 years with relapsed or refractory AML after ≤ 2 prior induction regimens, at least one containing anthracyclines
- Medically eligible to receive MEC
- Absolute blast count (ABC) ≤ 40,000/mm
For treatment-naïve subjects only:
- Subjects ≥ 60 years of age with newly diagnosed AML
- Medically eligible to receive "7+3" cytarabine/idarubicin
- ABC count ≤ 40,000/mm
- ECOG performance status 0-2
- Hemodynamically stable and adequate organ function
Exclusion criteria:
- Acute promyelocytic leukemia
- Acute leukemia of ambiguous lineage (biphenotypic leukemia)
- Active signs or symptoms of CNS involvement by malignancy
- No prior G-CSF, GM-CSF or plerixafor within 14 days of study drug dosing
- Known history or evidence of active hepatitis A, B, or C or HIV
- Uncontrolled acute life threatening bacterial, viral or fungal infection
- Active graft versus host disease (GVHD) ≥ Grade 2 or extensive chronic GVHD requiring immunosuppressive therapy
- Hematopoietic stem cell transplantation ≤ 4 months of dosing
- Clinically significant cardiovascular disease
Sites / Locations
- University of California, Davis Comprehensive Cancer Center
- Dana Farber Cancer Institute
- University of Michigan, Ann Arbor
- University of Rochester
- Cleveland Clinic
- University of Washington
- Princess Alexandra Hospital
- University Hospital Galway
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Arm A (Phase I)
Arm B (Phase II Arm A)
Arm C (Phase II Arm B)
Arm Description
GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older
GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older
GMI-1271 in combination with cytarabine and idarubicin (7+3 regimen) in newly diagnosed subjects 60 years and older
Outcomes
Primary Outcome Measures
Safety assessed by frequency, severity and relatedness of adverse events
Secondary Outcome Measures
Time versus plasma concentration profile of GMI-1271
Plasma concentration of GMI-1271
Overall response rate
Proportion of subjects who achieve a complete response (CR) or CR with incomplete blood count recovery (CRi) per local investigator assessment
Time to response
Time from date of first dose to first documentation of response
Duration of response
Time from date of first documented remission to the date of relapse or death from any cause, whichever occurs first
Event-free survival
Time from date of first dose to the date of treatment failure, relapse, or death from any cause, whichever occurs first
Overall survival
The probability of survival at 6 months (Phase 1) and 12 months (Phase 2), after the date of first dose of study drug
Full Information
NCT ID
NCT02306291
First Posted
December 1, 2014
Last Updated
May 13, 2019
Sponsor
GlycoMimetics Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02306291
Brief Title
Study to Determine Safety, Pharmacokinetics and Efficacy of GMI-1271 in Combination With Chemotherapy in AML
Official Title
A Phase I/II, Open-label Multicenter Trial to Determine Safety, Pharmacokinetics and Efficacy of GMI-1271 in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
March 2015 (Actual)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
May 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlycoMimetics Incorporated
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will evaluate GMI-1271, a specific E-selectin antagonist, in acute myeloid leukemia in combination with standard agents used to treat this disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute
Keywords
AML, Acute myeloid leukemia, E-selectin, relapse refractory, elderly newly diagnosed, induction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
91 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A (Phase I)
Arm Type
Experimental
Arm Description
GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older
Arm Title
Arm B (Phase II Arm A)
Arm Type
Experimental
Arm Description
GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older
Arm Title
Arm C (Phase II Arm B)
Arm Type
Experimental
Arm Description
GMI-1271 in combination with cytarabine and idarubicin (7+3 regimen) in newly diagnosed subjects 60 years and older
Intervention Type
Drug
Intervention Name(s)
GMI-1271
Other Intervention Name(s)
Uproleselan
Intervention Description
E-selectin antagonist
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Intervention Description
induction chemotherapy
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
induction chemotherapy
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
induction chemotherapy
Intervention Type
Drug
Intervention Name(s)
Idarubicin
Intervention Description
induction chemotherapy
Primary Outcome Measure Information:
Title
Safety assessed by frequency, severity and relatedness of adverse events
Time Frame
up to 44 days
Secondary Outcome Measure Information:
Title
Time versus plasma concentration profile of GMI-1271
Description
Plasma concentration of GMI-1271
Time Frame
up to 11 days
Title
Overall response rate
Description
Proportion of subjects who achieve a complete response (CR) or CR with incomplete blood count recovery (CRi) per local investigator assessment
Time Frame
up to 12 months
Title
Time to response
Description
Time from date of first dose to first documentation of response
Time Frame
up to 12 months
Title
Duration of response
Description
Time from date of first documented remission to the date of relapse or death from any cause, whichever occurs first
Time Frame
up to 12 months
Title
Event-free survival
Description
Time from date of first dose to the date of treatment failure, relapse, or death from any cause, whichever occurs first
Time Frame
up to 12 months
Title
Overall survival
Description
The probability of survival at 6 months (Phase 1) and 12 months (Phase 2), after the date of first dose of study drug
Time Frame
up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
AML (including secondary AML) diagnosed as per WHO criteria
For relapsed/refractory subjects only:
Subjects age ≥ 18 years with relapsed or refractory AML after ≤ 2 prior induction regimens, at least one containing anthracyclines
Medically eligible to receive MEC
Absolute blast count (ABC) ≤ 40,000/mm
For treatment-naïve subjects only:
Subjects ≥ 60 years of age with newly diagnosed AML
Medically eligible to receive "7+3" cytarabine/idarubicin
ABC count ≤ 40,000/mm
ECOG performance status 0-2
Hemodynamically stable and adequate organ function
Exclusion criteria:
Acute promyelocytic leukemia
Acute leukemia of ambiguous lineage (biphenotypic leukemia)
Active signs or symptoms of CNS involvement by malignancy
No prior G-CSF, GM-CSF or plerixafor within 14 days of study drug dosing
Known history or evidence of active hepatitis A, B, or C or HIV
Uncontrolled acute life threatening bacterial, viral or fungal infection
Active graft versus host disease (GVHD) ≥ Grade 2 or extensive chronic GVHD requiring immunosuppressive therapy
Hematopoietic stem cell transplantation ≤ 4 months of dosing
Clinically significant cardiovascular disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel DeAngelo, MD, PhD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan, Ann Arbor
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Princess Alexandra Hospital
City
Brisbane
Country
Australia
Facility Name
University Hospital Galway
City
Galway
Country
Ireland
12. IPD Sharing Statement
Citations:
PubMed Identifier
34543383
Citation
DeAngelo DJ, Jonas BA, Liesveld JL, Bixby DL, Advani AS, Marlton P, Magnani JL, Thackray HM, Feldman EJ, O'Dwyer ME, Becker PS. Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia. Blood. 2022 Feb 24;139(8):1135-1146. doi: 10.1182/blood.2021010721.
Results Reference
derived
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Study to Determine Safety, Pharmacokinetics and Efficacy of GMI-1271 in Combination With Chemotherapy in AML
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