A Study Evaluating the Safety and Pharmacokinetics of Atezolizumab Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid Leukemia

NCT ID: NCT03922477

Last Updated: 2022-02-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-08
• Study Completion Date: 2020-11-03

Brief Summary

This Phase Ib study is designed to evaluate the safety and pharmacokinetics of atezolizumab when given in combination with Hu5F9-G4 to patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezolizumab + Hu5F9-G4

An initial safety evaluation will be performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 is initially safe and tolerable in participants an additional cohort with R/R AML will be evaluated to further test the safety and anti-tumor activity. If dose-limiting toxicities (DLT) are observed in \>=33% of participants in this initial cohort, a dose de-escalation cohort will be enrolled. If less than 33% of enrolled and dosed participants in any given cohort experience a DLT, an expansion cohort of 15 participants will be enrolled at the highest tolerated dose for this combination. If a dose de-escalation cohort is needed, an expansion cohort will be enrolled at the lower tolerated dose for this combination.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered to participants by IV infusion at a fixed dose starting on Day 22 of Cycle 1. In subsequent cycles (Cycles 2 and beyond), IV atezolizumab will be given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle.

Hu5F9-G4

Intervention Type: DRUG

Two priming doses of 1 mg/kg of Hu5F9-G4 will be administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance will be given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle. Dosing for de-escalation, if needed: Hu5F9-G4 will be given as two priming doses of 1 mg/kg IV on Days 1 and 4, followed by loading doses of 10 mg/kg IV on Day 8 and 15 mg/kg on Day 11. Starting on Day 15, maintenance treatment with Hu5F9-G4 will be given by IV infusion at a dose of 15 mg/kg once a week (QW).

Interventions

Atezolizumab

Atezolizumab will be administered to participants by IV infusion at a fixed dose starting on Day 22 of Cycle 1. In subsequent cycles (Cycles 2 and beyond), IV atezolizumab will be given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle.

Intervention Type: DRUG

Hu5F9-G4

Two priming doses of 1 mg/kg of Hu5F9-G4 will be administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance will be given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle. Dosing for de-escalation, if needed: Hu5F9-G4 will be given as two priming doses of 1 mg/kg IV on Days 1 and 4, followed by loading doses of 10 mg/kg IV on Day 8 and 15 mg/kg on Day 11. Starting on Day 15, maintenance treatment with Hu5F9-G4 will be given by IV infusion at a dose of 15 mg/kg once a week (QW).

Intervention Type: DRUG

Other Intervention Names

Tecentriq

Eligibility Criteria

Inclusion Criteria

• Life expectancy of at least 12 weeks
• Eastern Cooperative Oncology Group Performance Status 0-2
• Documented and confirmed R/R AML per WHO classification, except acute promyelocytic leukemia, and lack of response to all therapies of known benefit
• Adequate end-organ function
• Negative HIV test at screening
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA <500 IU/mL at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
• Willingness and ability to provide pretreatment bone marrow aspirate and biopsy and agreement to provide subsequent bone marrow aspirates and biopsies during study treatment
• For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
• For women who are not postmenopausal or surgically sterile: requirement for a negative serum pregnancy test result within 14 days prior to initiation of study treatment

Exclusion Criteria

• Previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease, or requiring transplant-related immunosuppression
• Prior solid organ transplant
• Evidence of active central nervous system (CNS) involvement by leukemia
• Pregnancy or lactation or intention to become pregnant during the study or within 5 months after the final dose of atezolizumab and/or Hu5F9-G4, whichever is longer
• History of idiopathic pulmonary fibrosis, organizing pneumonitis, drug-induced pneumonitis, or idiopathic pneumonitis
• History of autoimmune disease. Patients with a history of autoimmune-related hypothyroidism who are on a stable dose of thyroid replacement may be eligible for this study. Patients with controlled Type 1 diabetes mellitus who are on a stable insulin regimen may be eligible for this study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of the following conditions are met: (1) Rash must cover <10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition that require psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• Treatment with investigational therapy within 14 days prior to initiation of study drug
• Any approved AML-related therapy within 14 days prior to enrollment. Granulocyte colony-stimulating factor to treat neutropenic fever and/or infection is permitted. Hydroxyurea may be used throughout the trial to control peripheral blood blast counts in response to the first dose of study treatment and during the first 4 weeks of study treatment.

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

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Yale

New Haven, Connecticut, United States

Columbia University

New York, New York, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

GO40828

Identifier Type: -

Identifier Source: org_study_id