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)

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Fludarabine; Drug: Melphalan; Drug: vadastuximab talirine; Drug: vadastuximab talirine

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago
  • Kansas
    • Westwood, Kansas, United States, United States
      • University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University / University Hospitals Case Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4095
      • MD Anderson Cancer Center / University of Texas
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-allo (before stem cell transplant); Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine)	Drug: Fludarabine; 30 mg/m2/day intravenously, 5 to 2 days before the transplant (total dose of 120 mg/m2); Drug: Melphalan; Melphalan 140 mg/m2 intravenously, 2 days before the transplant; Drug: vadastuximab talirine; Pre-allo (before stem cell transplant) given 14 days before the stem cell transplant; Drug: vadastuximab talirine; Post-allo (after stem cell transplant) given on Day 1 of each cycle
Experimental: Post-allo (after stem cell transplant); Post-allo vadastuximab talirine	Drug: vadastuximab talirine; Pre-allo (before stem cell transplant) given 14 days before the stem cell transplant; Drug: vadastuximab talirine; Post-allo (after stem cell transplant) given on Day 1 of each cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	9 weeks
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.	9 weeks
Overall Survival	Defined as the time from the day of alloSCT to the date of death due to any cause.	Approximately 96 weeks

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Director: Phillip Garfin, MD, PhD, Seagen Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): February 10, 2017
• Study Completion (Actual): September 14, 2017

Study Registration Dates

• First Submitted: November 20, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: AML; acute myeloid leukemia; antibody-drug conjugate
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Fludarabine
• Other Study ID Numbers: SGN33A-003