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.

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