Clinical trial NCT03922477: 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
Official title: A Phase Ib, Open-Label Study Evaluating the Safety and Pharmacokinetics of Atezolizumab (Anti-PD-L1 Antibody) Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-04-22
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Up to approximately 13 months after first participant enrolled
measure: Complete Remission (CR)
timeFrame: Up to approximately 3 months after first participant enrolled
measure: Duration of Response (DOR)
timeFrame: Up to approximately 3 months after first particpant enrolled
Secondary outcomes:
measure: Serum Concentrations of Atezolizumab
timeFrame: C1 D22 PTFI of Hu5F9-G4 and atezolizumab, and 30 minutes after atezolizumab infusion; C2 D8 PTFI; C2 D22 PTFI; C3 D22 PTFI; C4 D22 PTFI; C8 D22 PTFI; C12 D22 PTFI; C16 D22 PTFI; TDV (up to C16 D21);120 days after final dose of atezolizumab (UTA 37M)
measure: Serum Concentrations of Hu5F9-G4
timeFrame: C1D1 PTFI&1H AEOI; C1D8 PTFI,&1H AEOI; C1D11 PTFI,&1H AEOI; C1D22 1H AEOI; C2D1 PTFI,&1H AEOI; C2D8 PTFI; C3D1 PTFI,&1H AEOI; C5D1 PTFI; C7D1 PTFI, C9D1 PTFI; C11D1 PTFI; C13D1 PTFI; C15D1 PTFI; C17D1&D1 E 2C T PTFI(UTA 37M);TDV(up to C16D21)(UTA 37M)
measure: Objective Response Rate
timeFrame: Up to approximately 3 months after first participant enrolled
measure: Event-Free Survival
timeFrame: Up to approximately 3 months after first participant enrolled
measure: Leukemia-Free Survival
timeFrame: Up to approximately 3 months after first participant enrolled
measure: Overall Survival
timeFrame: Up to approximately 13 months after first participant enrolled
measure: Progression-Free Survival
timeFrame: Up to approximately 3 months after first participant enrolled
measure: Rate of Transfusion Independence
timeFrame: Up to approximately 3 months after first participant enrolled
measure: Duration of Transfusion Independence
timeFrame: Up to approximately 3 months after first participant enrolled
measure: Incidence of Anti-Drug Antibodies (ADAs) Against Atezolizumab During the Study Relative to the Prevalence of ADAs at Baseline
timeFrame: Baseline up to approximately 37 months
measure: Incidence of ADAs Against Hu5F9-G4 During the Study Relative to the Prevalence of ADAs at Baseline
timeFrame: Baseline up to approximately 37 months
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale
state: Connecticut
city: New York
country: United States
facility: Columbia University
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: