A Study of Vadastuximab Talirine Given Prior to or After Allogeneic Hematopoietic Stem Cell Transplant in AML Patients
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)
1 other identifier
interventional
14
1 country
11
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2015
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2015
CompletedFirst Submitted
Initial submission to the registry
November 20, 2015
CompletedFirst Posted
Study publicly available on registry
November 25, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 10, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
September 14, 2017
CompletedResults Posted
Study results publicly available
January 9, 2019
CompletedJanuary 9, 2019
December 1, 2018
1.3 years
November 20, 2015
September 5, 2018
December 20, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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.
Approximately 1 year
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.
Approximately 1 year
1-year Survival Rate
1-year survival rate estimated using Kaplan-Meier methods The start date for overall survival is the day of alloSCT.
12 months
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)
30 days
Secondary Outcomes (3)
Best Response of CR or CRi
9 weeks
Duration of Response
9 weeks
Overall Survival
Approximately 96 weeks
Study Arms (2)
Pre-allo (before stem cell transplant)
EXPERIMENTALPre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)
Post-allo (after stem cell transplant)
EXPERIMENTALPost-allo vadastuximab talirine
Interventions
30 mg/m2/day intravenously, 5 to 2 days before the transplant (total dose of 120 mg/m2)
Melphalan 140 mg/m2 intravenously, 2 days before the transplant
Pre-allo (before stem cell transplant) given 14 days before the stem cell transplant
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Seagen Inc.lead
Study Sites (11)
City of Hope National Medical Center
Duarte, California, 91010-3000, United States
Colorado Blood Cancer Institute
Denver, Colorado, 80218, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612, United States
University of Chicago
Chicago, Illinois, 60637-1470, United States
University of Kansas Cancer Center
Westwood, Kansas, United States, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10021, United States
Weill Cornell Medical College
New York, New York, 10065, United States
Case Western Reserve University / University Hospitals Case Medical Center
Cleveland, Ohio, 44106, United States
MD Anderson Cancer Center / University of Texas
Houston, Texas, 77030-4095, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
No patients were enrolled in Phase 2 due to study termination.
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Seattle Genetics, Inc.
Study Officials
- STUDY DIRECTOR
Phillip Garfin, MD, PhD
Seagen Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 20, 2015
First Posted
November 25, 2015
Study Start
November 1, 2015
Primary Completion
February 10, 2017
Study Completion
September 14, 2017
Last Updated
January 9, 2019
Results First Posted
January 9, 2019
Record last verified: 2018-12