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Clinical Trial 19322

Cancer Type: Malignant Hematology
Interventions:Hu5F9-G4 (); azacitidine (5-azacitidine)

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • David Sallman

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase 1b Trial of Hu5F9-G4 Monotherapy or Hu5F9-G4 in Combination with Azacitidine in Patients with Hematological Malignancies

Summary

The purpose of this study is to test the safety of Hu5F9-G4 in participants with blood cancers such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Other purposes of this study are to determine the best dose of Hu5F9-G4, the quantity of Hu5F9-G4 in the participant's blood, the side effects it has on their body, and whether or not it can improve their cancer. Potential participants are being asked to take part in this study because they have been diagnosed with blood cancer and the anti-cancer therapy that they have received so far has not worked.

Objective

Primary Objectives: To confirm the safety and tolerability of Hu5F9-G4 monotherapy in this relapsed/refractory AML and MDS population, and of Hu5F9-G4 in combination with azacitidine in previously untreated AML and MDS. To evaluate the efficacy of Hu5F9-G4 monotherapy in relapsed/refractory AML/MDS, and of Hu5F9-G4 in combination with azacitidine in previously untreated AML/MDS, as measured by the objective response rate (ORR). Secondary Objectives: To evaluate the pharmacokinetic (PK) profile of Hu5F9-G4 alone and in combination with azacitidine. To evaluate the immunogenicity of Hu5F9-G4. To evaluate the efficacy of Hu5F9-G4 alone or in combination with azacitidine as measured by the duration of response (DOR), progression-free survival (PFS), relapse-free survival (RFS), and overall survival (OS). Exploratory Objectives: To assess CD47 receptor occupancy. To assess biomarkers of immune cell efficacy and bone marrow penetration of Hu5F9-G4. To assess efficacy in molecular subtypes of AML/MDS.

Inclusion Criteria

  • Meets the criteria below for the appropriate cohort:
  • a) All R/R Cohorts: >i. Pathologically confirmed AML (defined by 2017 European Leukemia Net [ELN] classification) relapsed or refractory to a prior therapy with either a hypomethylating agent (such as azacitidine or decitabine), non-intensive chemotherapy (such as low-dose cytarabine arabinoside), and/or venetoclax. Treatment is limited to 1 prior line of therapy. Hematopoietic stem cell transplant for patients in remission would not be counted as a line of therapy for AML, or
  • ii. Confirmed MDS defined according to World Health Organization (WHO) classification that is either refractory to hypomethylating agent (defined as disease progression per the International Working Group [IWG] MDS response criteria at any time after initiation of a hypomethylating agent or failure to achieve an objective response by IWG 2006 criteria after 4 cycles) or is relapsed or intolerant to prior therapy with either a hypomethylating agent, non-intensive chemotherapy, or targeted therapy. Treatment is limited to 1 prior line of hypomethylating agent therapy (including investigational hypomethylating agents) for all R/R MDS patients.
  • b) All TN/U Cohorts (meets i or ii):
  • i. Previously untreated patients with MDS defined according to WHO classification, with an IPSS-R risk category of intermediate, high, or very high risk. Prior and concurrent therapy with hydroxyurea, oral etoposide, erythroid and/or myeloid growth factors is allowed.
  • ii. Previously untreated patients with histological confirmation of AML by WHO criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity, age or other factors, or who refuse such therapy; or
  • c) Rollover Cohort: Patients on active Hu5F9-G4 therapy on the Phase 1 AML (SCI-CD47-002) trial who are deriving clinical benefit by Investigator assessment.
  • 2. White blood cell (WBC) count ≤ 20 × 103/mcL pre-first dose of study treatment and prior to each Hu5F9-G4 dose for Cycle 1. Patients with WBC > 20 × 103/mcL can be treated with hydroxyurea (up to 4 g/day) throughout the trial to reduce the WBC to ≤ 20 × 103/mcL. Oral etoposide (up to 200 mg orally [PO] /day) may be given as an alternative to hydroxyurea for patients who are intolerant to hydroxyurea or cannot achieve sufficient WBC lowering on hydroxyurea.

  • Exclusion Criteria

  • Prior treatment with CD47 or signal regulatory protein alpha (SIRPα) targeting agents (with exception of Hu5F9-G4 for patients in the Rollover cohort).
  • Treatment-naïve/Unfit Cohorts Only: Any prior anti-leukemic therapy (excluding hydroxyurea or oral etoposide), prior treatment with hypomethylating agents and/or low dose cytarabine.
  • Acute promyelocytic leukemia.
  • Known inherited or acquired bleeding disorders.
  • Previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease (GVHD), or requiring transplant-related immunosuppression.
  • Clinical suspicion of active central nervous system (CNS) involvement by leukemia
  • Known active or chronic hepatitis B or C infection or HIV
  • Pregnancy or active breastfeeding