A Study of Vadastuximab Talirine Given Prior to or After Allogeneic Hematopoietic Stem Cell Transplant in AML Patients

Phase 1

Terminated

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Fludarabine; Drug: Melphalan; Drug: vadastuximab talirine

• Registration Number: NCT02614560
• Lead Sponsor: Seagen Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11
• Study First Submitted: 2015-11-20
• Study First Submitted QC: 2015-11-23
• Study First Posted: 2015-11-25
• Primary Completion: 2017-02-10
• Study Completion: 2017-09-14
• Disposition First Submitted: 2018-01-03
• Disposition First Submitted QC: 2018-01-03
• Disposition First Posted: 2018-01-05
• Results First Submitted: 2018-09-05
• Status Verified: 2018-12
• Results First Submitted QC: 2018-12-20
• Last Update Submitted: 2018-12-20
• Results First Posted: 2019-01-09
• Last Update Posted: 2019-01-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pre-allo (before stem cell transplant)	Fludarabine	Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)
Pre-allo (before stem cell transplant)	vadastuximab talirine	Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)
Pre-allo (before stem cell transplant)	Melphalan	Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)
Post-allo (after stem cell transplant)	vadastuximab talirine	Post-allo vadastuximab talirine

Primary Outcome Measures

Name	Time	Method
Rate of MRD Negativity	30 days	Rate of MRD (minimal residual disease) negativity at Day -1 (1 day prior to transplant) and Day 30 post-transplant (Part A only)
Incidence of Laboratory Abnormalities	Approximately 1 year	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.
Incidence of Adverse Events	Approximately 1 year	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.
1-year Survival Rate	12 months	1-year survival rate estimated using Kaplan-Meier methods The start date for overall survival is the day of alloSCT.

Secondary Outcome Measures

Name	Time	Method
Best Response of CR or CRi	9 weeks	Percentage of patients who achieved a best response of CRi (complete remission with incomplete blood count recovery) or CR (complete remission)
Duration of Response	9 weeks	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	Approximately 96 weeks	Defined as the time from the day of alloSCT to the date of death due to any cause.

Trial Locations

Locations (11)

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

H. Lee Moffitt Cancer Center & Research Institute; 🇺🇸 Tampa, Florida, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Case Western Reserve University / University Hospitals Case Medical Center; 🇺🇸 Cleveland, Ohio, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

University of Kansas Cancer Center; 🇺🇸 Westwood, Kansas, United States

MD Anderson Cancer Center / University of Texas; 🇺🇸 Houston, Texas, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States