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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
Active, not recruiting
Conditions
Acute Myeloid Leukemia
Interventions
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
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
18
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Gemtuzumab Ozogamicin(GO) + VenetoclaxGemtuzumab OzogamicinGemtuzumab Ozogamicin(GO) + Venetoclax
Gemtuzumab Ozogamicin(GO) + VenetoclaxVenetoclaxGemtuzumab Ozogamicin(GO) + Venetoclax
Primary Outcome Measures
NameTimeMethod
Maximum Tolerated Dose (MTD) of Venetoclax when administered with GO42 days

Assess the maximum tolerated dose (MTD) of Venetoclax when administered with GO in patients with AML.

-Dose-limiting toxicity, 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); 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).

Secondary Outcome Measures
NameTimeMethod
Rate of Anti-leukemic activity7 months

Anti-leukemic activity (CR/Cri/PR), as defined by the revised IWG criteria

Relapse-free survival7 months

patients achieving CR or CRi; measured from the date of achievement of a remission until the date of relapse or death from any cause; patients not known to have relapsed or died at last follow-up are censored on the date they were last examined

Overall response rate7 months

Overall response rate (CR/CRi), as defined by the revised IWG criteria

Event-free Survival7 months

Event-free Survival will be measured from the date of entry to the date of treatment failure, disease relapse, or death from any cause; patients not known to have any of these events are censored on the date they were last examined

overall survival7 months

Overall survival will be measured from the date of entry to the date of 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

🇺🇸

Omaha, Nebraska, United States

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Univeristy of Illinois

🇺🇸

Chicago, Illinois, United States

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