Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113

Phase 1

Completed

Conditions: Acute Myeloid Leukemia

Interventions: Drug: Gemtuzumab Ozogamicin
Drug: Venetoclax

Registration Number: NCT04070768

Lead Sponsor: John Quigley

Brief Summary: This is a Phase Ib Study to determine the Maximum Tolerated Dose (MTD) of Venetoclax in combination with Gemtuzumab Ozogamicin(GO) in subjects with relapsed/refractory acute myeloid leukemia. Using a standard 3+3 design, subjects will receive once cycle of combination therapy. After one cycle of combination therapy, subjects showing response will continue on to one cycle of consolidation therapy with GO\\Veneoclax. Subjects who respond to combination therapy will continue on maintenance Venetoclax until progression or unacceptable toxicity.

Dose-limiting toxicity, defined as an adverse event related (possible, probably, or definite) to Venetoclax and/or Gemtuzumab fulfilling one of the following criteria:

criteria:

* Hematologic toxicity: treatment-related grade 3 or worse neutropenia and/or thrombocytopenia due to bone marrow hypocellularity present at the end of cycle one (day 28) with an additional 28 days allowed for count recovery (i.e. present at day 56); specifically grade 3 or worse neutropenia or thrombocytopenia with the bone marrow documented to be free of leukemic infiltration. Note: patients who enter the study with grade 3 or worse cytopenias will not be evaluable for hematologic dose-limiting toxicities.

* Non-hematologic toxicity: any grade 3 or worse treatment-related toxicity occurring within the first cycle (excluding grade 3-4 infections during cycle one).

The study will also evaluate the Overall Response Rate, Anti-leukemic activity, Relapse-free Survival (RFS), event-free survival (EFS) , and overall survival (OS). The study will evaluate quality of life using the European Organization for the Research and Treatment of Cancer 30 item questionnaire (EORTC QLQ-C30).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gemtuzumab Ozogamicin(GO) + Venetoclax	Gemtuzumab Ozogamicin	Gemtuzumab Ozogamicin(GO) + Venetoclax
Gemtuzumab Ozogamicin(GO) + Venetoclax	Venetoclax	Gemtuzumab Ozogamicin(GO) + Venetoclax

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of Venetoclax When Administered With Gemtuzumab Ozogamicin (GO)	42 days	MTD was determined by testing increasing doses up to 600mg orally daily on dose escalation cohorts 1 to 3 with 3 to 6 participants each. MTD reflects the highest dose of drug where fewer than 33% of subjects experience a dose limiting toxicity (DLT). DLT is defined as an adverse event related (possible, probably, or definite) to Venetoclax and/or Gemtuzumab fulfilling one of the following criteria: Hematologic toxicity: treatment-related grade 3 or worse neutropenia and/or thrombocytopenia due to bone marrow hypocellularity present at the end of cycle one (day 28) with an additional 28 days allowed for count recovery (i.e. present at day 56); Note: patients who enter the study with grade 3 or worse cytopenias will not be evaluable for hematologic DLT. Non-hematologic toxicity: any grade 3 or worse treatment-related toxicity occurring within the first 56 days.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	Up to 7 months	Per International Working Group Criteria (IWGC), Complete remission (CR): Bone marrow blasts \< 5%; absence of blasts with Auer rods and extramedullary disease; absolute neutrophil count \> 1.0 x 109/L(1000/μL); platelet count \> 100 x 109/L (100,000/μL); independent of red cell transfusions. CR with incomplete recovery (CRi): All CR criteria except for residual neutropenia \< 1.0 x 109/L(1000/μL) or thrombocytopenia \< 100 x 109/L (100,000/μL). Overall response rate = CR + CRi
Anti-leukemic Activity Rate	Up to 7 months	Per International Working Group Criteria (IWGC), Complete remission (CR): Bone marrow blasts \< 5%; absence of blasts with Auer rods and extramedullary disease; absolute neutrophil count \> 1.0 x 109/L(1000/μL); platelet count \> 100 x 109/L (100,000/μL); independent of red cell transfusions. CR with incomplete recovery (CRi): All CR criteria except for residual neutropenia \< 1.0 x 109/L(1000/μL) or thrombocytopenia \< 100 x 109/L (100,000/μL). Partial remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%. Anti-leukemic activity Rate =CR+Cri+PR
Relapse-free Survival	Up to 7 months	Per International Working Group Criteria (IWGC), Complete remission (CR): Bone marrow blasts \< 5%; absence of blasts with Auer rods and extramedullary disease; absolute neutrophil count \> 1.0 x 109/L(1000/μL); platelet count \> 100 x 109/L (100,000/μL); independent of red cell transfusions. CR with incomplete recovery (CRi): All CR criteria except for residual neutropenia \< 1.0 x 109/L(1000/μL) or thrombocytopenia \< 100 x 109/L (100,000/μL). Relapse: Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood; or development of extramedullary disease. Relapse-free survival is defined as the time from achievement of a remission until the relapse or death from any cause in patients achieving CR or CRi. Patients not known to have relapsed or died at last follow-up are censored on the date they were last examined
Event-free Survival	7 months	Event-free Survival is defined as the time from on study to treatment failure, disease relapse, or death from any cause. Patients not known to have any of these events are censored on the date of last examined.
Overall Survival (OS)	Up to 8 months	Overall survival is defined as the time from study entry to death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.

Trial Locations

Locations (4): University of Michigan Health System
🇺🇸
Ann Arbor, Michigan, United States
University of Nebraska Medical Center
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Omaha, Nebraska, United States
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Univeristy of Illinois
🇺🇸
Chicago, Illinois, United States