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

Acute Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02614560
• Other study ID #: SGN33A-003
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 2015
• Est. completion date: September 14, 2017

Study information

• Verified date: December 2018
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: September 14, 2017
• Est. primary completion date: February 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Fludarabine
30 mg/m2/day intravenously, 5 to 2 days before the transplant (total dose of 120 mg/m2)
• Melphalan
Melphalan 140 mg/m2 intravenously, 2 days before the transplant
• vadastuximab talirine
Pre-allo (before stem cell transplant) given 14 days before the stem cell transplant
• vadastuximab talirine
Post-allo (after stem cell transplant) given on Day 1 of each cycle

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Case Western Reserve University / University Hospitals Case Medical Center	Cleveland	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Overall Survival	Defined as the time from the day of alloSCT to the date of death due to any cause.	Approximately 96 weeks