Back to resultsA Study of Vadastuximab Talirine Given Prior to or After Allogeneic Hematopoietic Stem Cell Transplant in AML Patients
Primary Purpose
Acute Myeloid Leukemia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Melphalan
vadastuximab talirine
vadastuximab talirine
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring acute myeloid leukemia, AML, antibody-drug conjugate
Eligibility Criteria
Inclusion Criteria:
- Relapsed/refractory acute myeloid leukemia (AML) except for acute promyelocytic leukemia
- Eastern Cooperative Oncology Group status of 0 or 1
- Adequate baseline renal and hepatic function
- For Pre-allo Part A (before stem cell transplant): Relapsed or refractory AML (greater than 5% blasts)
- For Pre-allo Part A (before stem cell transplant): Availability of an HLA matched related or unrelated donor
- For Pre-allo Part A (before stem cell transplant): Eligible for an allogeneic hematopoietic stem cell transplant
- For Post-allo Part B: Transplant must have been performed with active AML (greater than 5% blasts) using a conventional conditioning regimen and have achieved CR or CRi post-alloSCT (with ANC greater than or equal to 1,000 and platelet greater than or equal to 50,000)
- For Post-allo Part B: Treatment must begin at least 42 days, but no more than 100 days post-transplant.
Exclusion Criteria:
- Inadequate heart function
- Inadequate lung function
- Previous central nervous system leukemia
- Any history of another metastatic malignancy
- Anti-leukemia treatment within14 days of study drug (other than hydroxyurea or 6-mercaptopurine), immunosuppressive therapy (except for GVHD treatment/prophylaxis in Part B), or investigational agents
- For Pre-allo Part A (before stem cell transplant): Partially matched donors (related or unrelated) and umbilical cord blood cells are excluded as the source of hematopoietic stem cells
- For Pre-allo Part A (before stem cell transplant): Prior alloSCT
- For Post-allo Part B: Active GVHD Grade 2 or higher
- For Post-allo Part B:History of veno-occlusive disease requiring defibrotide
- For Post-allo Part B: History of Grade 2 or higher hepatic GVHD
- For Post-allo Part B: Concurrent use of corticosteroids equivalent of prednisone at a dose of greater than 0.5 mg/kg
Sites / Locations
- City of Hope National Medical Center
- Colorado Blood Cancer Institute
- H. Lee Moffitt Cancer Center & Research Institute
- University of Chicago
- University of Kansas Cancer Center
- Dana Farber Cancer Institute
- Memorial Sloan Kettering Cancer Center
- Weill Cornell Medical College
- Case Western Reserve University / University Hospitals Case Medical Center
- MD Anderson Cancer Center / University of Texas
- Fred Hutchinson Cancer Research Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Pre-allo (before stem cell transplant)
Post-allo (after stem cell transplant)
Arm Description
Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)
Post-allo vadastuximab talirine
Outcomes
Primary Outcome Measures
Incidence of Adverse Events
AE: Adverse events; TEAE: Treatment-emergent adverse event. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event. An AE is considered serious if it was fatal, life threatening, required hospitalization, was disabling/incapacitating, resulted in a birth defect or congenital anomally, or was otherwise considered to be medically significant.
Incidence of Laboratory Abnormalities
Number (count) of participants that experienced a Grade 3 or higher laboratory toxicity (hematology and chemistry). Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event.
1-year Survival Rate
1-year survival rate estimated using Kaplan-Meier methods The start date for overall survival is the day of alloSCT.
Rate of MRD Negativity
Rate of MRD (minimal residual disease) negativity at Day -1 (1 day prior to transplant) and Day 30 post-transplant (Part A only)
Secondary Outcome Measures
Best Response of CR or CRi
Percentage of patients who achieved a best response of CRi (complete remission with incomplete blood count recovery) or CR (complete remission)
Duration of Response
Defined as the time from the start of the first documented complete response (CR) or complete remission with incomplete blood count recovery (CRi) to the documentation of relapse or death due to any cause.
Overall Survival
Defined as the time from the day of alloSCT to the date of death due to any cause.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02614560
Brief Title
A Study of Vadastuximab Talirine Given Prior to or After Allogeneic Hematopoietic Stem Cell Transplant in AML Patients
Official Title
A Phase 1/2 Study of Vadastuximab Talirine Administered in Sequence With Allogeneic Hematopoietic Stem Cell Transplant in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Study Start Date
November 2015 (undefined)
Primary Completion Date
February 10, 2017 (Actual)
Study Completion Date
September 14, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seagen Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will examine the safety and anti-leukemic profile of SGN-CD33A (vadastuximab talirine) in patients with relapsed chemo-resistant AML, who are given vadastuximab talirine in sequence with standard treatments before a planned stem cell transplant, or as maintenance therapy after a stem cell transplant. The main purpose of the study is to find the best dose and determine the anti-leukemic activity of vadastuximab talirine, given either pre- or post-allogeneic stem cell transplant (alloSCT) for adults with relapsed or refractory AML. This will be determined by assessing the safety and tolerability of vadastuximab talirine. In addition, the pharmacokinetic profile and anti-leukemic activity of the study treatment will be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
acute myeloid leukemia, AML, antibody-drug conjugate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pre-allo (before stem cell transplant)
Arm Type
Experimental
Arm Description
Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)
Arm Title
Post-allo (after stem cell transplant)
Arm Type
Experimental
Arm Description
Post-allo vadastuximab talirine
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
30 mg/m2/day intravenously, 5 to 2 days before the transplant (total dose of 120 mg/m2)
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
Melphalan 140 mg/m2 intravenously, 2 days before the transplant
Intervention Type
Drug
Intervention Name(s)
vadastuximab talirine
Intervention Description
Pre-allo (before stem cell transplant) given 14 days before the stem cell transplant
Intervention Type
Drug
Intervention Name(s)
vadastuximab talirine
Intervention Description
Post-allo (after stem cell transplant) given on Day 1 of each cycle
Primary Outcome Measure Information:
Title
Incidence of Adverse Events
Description
AE: Adverse events; TEAE: Treatment-emergent adverse event. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event. An AE is considered serious if it was fatal, life threatening, required hospitalization, was disabling/incapacitating, resulted in a birth defect or congenital anomally, or was otherwise considered to be medically significant.
Time Frame
Approximately 1 year
Title
Incidence of Laboratory Abnormalities
Description
Number (count) of participants that experienced a Grade 3 or higher laboratory toxicity (hematology and chemistry). Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event.
Time Frame
Approximately 1 year
Title
1-year Survival Rate
Description
1-year survival rate estimated using Kaplan-Meier methods The start date for overall survival is the day of alloSCT.
Time Frame
12 months
Title
Rate of MRD Negativity
Description
Rate of MRD (minimal residual disease) negativity at Day -1 (1 day prior to transplant) and Day 30 post-transplant (Part A only)
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Best Response of CR or CRi
Description
Percentage of patients who achieved a best response of CRi (complete remission with incomplete blood count recovery) or CR (complete remission)
Time Frame
9 weeks
Title
Duration of Response
Description
Defined as the time from the start of the first documented complete response (CR) or complete remission with incomplete blood count recovery (CRi) to the documentation of relapse or death due to any cause.
Time Frame
9 weeks
Title
Overall Survival
Description
Defined as the time from the day of alloSCT to the date of death due to any cause.
Time Frame
Approximately 96 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Relapsed/refractory acute myeloid leukemia (AML) except for acute promyelocytic leukemia
Eastern Cooperative Oncology Group status of 0 or 1
Adequate baseline renal and hepatic function
For Pre-allo Part A (before stem cell transplant): Relapsed or refractory AML (greater than 5% blasts)
For Pre-allo Part A (before stem cell transplant): Availability of an HLA matched related or unrelated donor
For Pre-allo Part A (before stem cell transplant): Eligible for an allogeneic hematopoietic stem cell transplant
For Post-allo Part B: Transplant must have been performed with active AML (greater than 5% blasts) using a conventional conditioning regimen and have achieved CR or CRi post-alloSCT (with ANC greater than or equal to 1,000 and platelet greater than or equal to 50,000)
For Post-allo Part B: Treatment must begin at least 42 days, but no more than 100 days post-transplant.
Exclusion Criteria:
Inadequate heart function
Inadequate lung function
Previous central nervous system leukemia
Any history of another metastatic malignancy
Anti-leukemia treatment within14 days of study drug (other than hydroxyurea or 6-mercaptopurine), immunosuppressive therapy (except for GVHD treatment/prophylaxis in Part B), or investigational agents
For Pre-allo Part A (before stem cell transplant): Partially matched donors (related or unrelated) and umbilical cord blood cells are excluded as the source of hematopoietic stem cells
For Pre-allo Part A (before stem cell transplant): Prior alloSCT
For Post-allo Part B: Active GVHD Grade 2 or higher
For Post-allo Part B:History of veno-occlusive disease requiring defibrotide
For Post-allo Part B: History of Grade 2 or higher hepatic GVHD
For Post-allo Part B: Concurrent use of corticosteroids equivalent of prednisone at a dose of greater than 0.5 mg/kg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Phillip Garfin, MD, PhD
Organizational Affiliation
Seagen Inc.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
University of Kansas Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
United States
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Case Western Reserve University / University Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
MD Anderson Cancer Center / University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4095
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of Vadastuximab Talirine Given Prior to or After Allogeneic Hematopoietic Stem Cell Transplant in AML Patients
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