A Safety Study of SGN-CD33A in AML Patients

NCT ID: NCT01902329

Last Updated: 2018-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 195 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2017-12-08

Brief Summary

This study will examine the safety profile of vadastuximab talirine (SGN-CD33A) administered as a single agent and in combination with a hypomethylating agent (HMA). The main purpose of the study is to find the maximum tolerated dose (MTD, which is the highest dose that does not cause unacceptable side effects) of SGN-CD33A in patients with acute myeloid leukemia (AML). The MTD will be determined by observing the dose-limiting toxicities (the side effects that prevent further increases in dose) of SGN-CD33A. In addition, the pharmacokinetic profile and anti-leukemia activity of SGN-CD33A will be assessed.

Detailed Description

This study will explore SGN-CD33A as a monotherapy and in combination with a hypomethylating agent (HMA; i.e., azacitidine or decitabine). Initial study treatment with SGN-CD33A includes a maximum of 2 cycles of treatment for monotherapy and 4 cycles for combination cohorts. Patients who achieve documented CR or CRi (Monotherapy) or clinical benefit (Combination) during the first part of the study are eligible to continue treatment.

Additional monotherapy cohorts may include patients with relapsed acute promyelocytic leukemia, relapsed patients with nucleophosmin-1 gene mutation (absence of fms-like tyrosine kinase 3 mutation) (NPM1-mutated, FLT-3 wild type), alternate dosing schedules (fractionated dosing on Days 1 and 4), treatment naive patients with AML who declined intensive therapy, and patients who have relapsed after post-allogeneic stem cell transplant.

Patients in the combination cohort will be treated with azacitidine or decitabine per institutional practice prior to SGN-CD33A dosing. Expansion cohorts may be added for further evaluation of safety, pharmacokinetics, pharmacodynamics, and antitumor activity.

Conditions

Acute Myelogenous Leukemia; Acute Myeloid Leukemia; Acute Promyelocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SGN-CD33A + HMA

SGN-CD33A with hypomethylating agent

Group Type: EXPERIMENTAL

HMA

Intervention Type: DRUG

azacitidine 75 mg/m2 for 7 days or decitabine 20mg/m2 for 5 days

SGN-CD33A

Intervention Type: DRUG

Given intravenously on Day 1 or Days 1 and 4 every 3 weeks (SGN-CD33A Monotherapy) or given intravenously on the final HMA dosing day every 4 weeks (SGN-CD33A+HMA)

SGN-CD33A Monotherapy

SGN-CD33A

Group Type: EXPERIMENTAL

SGN-CD33A

Intervention Type: DRUG

Given intravenously on Day 1 or Days 1 and 4 every 3 weeks (SGN-CD33A Monotherapy) or given intravenously on the final HMA dosing day every 4 weeks (SGN-CD33A+HMA)

Interventions

HMA

azacitidine 75 mg/m2 for 7 days or decitabine 20mg/m2 for 5 days

Intervention Type: DRUG

SGN-CD33A

Given intravenously on Day 1 or Days 1 and 4 every 3 weeks (SGN-CD33A Monotherapy) or given intravenously on the final HMA dosing day every 4 weeks (SGN-CD33A+HMA)

Intervention Type: DRUG

Other Intervention Names

vadastuximab talirine

Eligibility Criteria

Inclusion Criteria

• Acute myeloid leukemia, positive for CD33
• Eastern Cooperative Oncology Group status of 0 or 1
• Adequate baseline renal and hepatic function
• Central venous access
• Either achieved complete remission (greater than 12 weeks in duration) with initial induction/consolidation and have experienced relapse of disease or declined treatment with high-dose induction/consolidation
• Bone marrow blasts greater than or equal to 5% for relapsed patients, or greater than or equal to 20% for untreated patients

Exclusion Criteria

• Inadequate lung function
• Prior allogeneic stem cell transplant, except for a specific cohort
• High-dose chemotherapy within 4 weeks of study drug
• Antileukemia treatment within 14 days of study drug (other than hydroxyurea or 6-mercaptopurine)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seagen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Phoenix Ho, MD

Role: STUDY_DIRECTOR

Seagen Inc.

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

City of Hope National Medical Center

Duarte, California, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Winship Cancer Institute / Emory University School of Medicine

Atlanta, Georgia, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Cleveland Clinic, The

Cleveland, Ohio, United States

Charles A. Sammons Cancer Center / Baylor University Medical Center

Dallas, Texas, United States

MD Anderson Cancer Center / University of Texas

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

References

Stein EM, Walter RB, Erba HP, Fathi AT, Advani AS, Lancet JE, Ravandi F, Kovacsovics T, DeAngelo DJ, Bixby D, Faderl S, Jillella AP, Ho PA, O'Meara MM, Zhao B, Biddle-Snead C, Stein AS. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood. 2018 Jan 25;131(4):387-396. doi: 10.1182/blood-2017-06-789800. Epub 2017 Dec 1.

Reference Type: DERIVED

PMID: 29196412 (View on PubMed)

Other Identifiers

SGN33A-001

Identifier Type: -

Identifier Source: org_study_id