This phase I/Ib trial studies the side effects and best dose of talazoparib given together with gemtuzumab ozogamicin and to see how well they work in treating patients with CD33 positive acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Talazoparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Gemtuzumab ozogamicin is a protein (antibody) combined with a chemotherapy drug which specifically targets acute myeloid leukemia cells expressing a marker (CD33). Adding talazoparib to the gemtuzumab ozogamicin therapy may lead to an increased effectiveness in treatment.
PRIMARY OBJECTIVES: I. Determine the safety and tolerability of talazoparib given in combination with gemtuzumab ozogamicin therapy in adult patients with relapsed and/or refractory acute myeloid leukemia (AML). II. Determine the overall response rate (ORR consisting of complete remission \[CR\] or complete remission with incomplete hematologic recovery \[CRi\]) of combination therapy with talazoparib and gemtuzumab ozogamicin in patients with relapsed and/or refractory AML. SECONDARY OBJECTIVE: I. Evaluate the preliminary anti-leukemic efficacy of talazoparib given in combination with gemtuzumab ozogamicin as determined by complete remission (CR) rate, best response rate (CRi + partial remission \[PR\]), duration of remission, leukemia-free survival (LFS), transfusion independence (TI), and overall survival (OS) in patients treated with this combination therapy. EXPLORATORY OBJECTIVES: I. Evaluate the efficacy of talazoparib given in combination with gemtuzumab ozogamicin on minimal residual disease (MRD) in treated patients. II. Evaluate mechanistic biomarkers including levels of PARP inhibition and deoxyribonucleic acid (DNA) damage effects in peripheral blood and marrow samples from patients treated with combination therapy. III. Evaluate quality of life (QOL) of patients with relapsed/refractory AML treated with talazoparib and gemtuzumab ozogamicin. IV. Evaluate the number of patients able to proceed onto subsequent hematopoietic stem cell transplantation (HSCT) following combination therapy. OUTLINE: This is a dose-escalation study of talazoparib. Patients receive talazoparib orally (PO) daily on days 1-21 and gemtuzumab ozogamicin intravenously (IV) over 2 hours on days 1, 4, and 7 or day 1 for patients who CR/CRi after cycles 1 or 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 12 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Maximum tolerated dose
Will identify the maximum tolerated dose of talazoparib in combination with gemtuzumab ozogamicin. The maximum dose level where 1 or fewer dose limiting toxicities (DLTs) are observed in 6 patients will be defined as the recommended phase 2 dose.
Time frame: Up to 28 days
Overall response rate (ORR)
ORR will consist of complete remission (CR), complete remission with incomplete hematologic recovery (CRi) of combination therapy with talazoparib and gemtuzumab ozogamicin. Will be estimated by a 90% confidence interval obtained by Jeffrey's prior method.
Time frame: Up to 12 months post treatment
Complete remission rate
The complete remission will be estimated with 90% confidence intervals obtained by Jeffrey's prior method.
Time frame: Up to 12 months post treatment
Best response rate
Best response rate will consist of CRi and partial remission (PR).
Time frame: Up to 12 months post treatment
Duration of remission
Duration of response will be estimated using standard Kaplan-Meier methods, where estimates of the median will be obtained with 90% confidence intervals.
Time frame: Up to 12 months post treatment
Leukemia-free survival (LFS)
LFS will be estimated using standard Kaplan-Meier methods, where estimates of the median will be obtained with 90% confidence intervals.
Time frame: Up to 12 months post treatment
Transfusion independence rate
Transfusion independence rate will be estimated with 90% confidence intervals obtained by Jeffrey's prior method.
Time frame: Up to 12 months post treatment
Hematopoietic stem cell transplantation (HSCT) rates
HSCT will be estimated with 90% confidence intervals obtained by Jeffrey's prior method.
Time frame: Up to 12 months post treatment
Overall survival (OS)
OS will be estimated using standard Kaplan-Meier methods, where estimates of the median will be obtained with 90% confidence intervals.
Time frame: Up to 12 months post treatment
Incidence of adverse events (AEs)
The observed AEs, serious AEs (SAEs), DLTs, and toxicities will be summarized by dose level and grade using frequencies and relative frequencies. AEs, SAEs, DLTs, and toxicity rates will be estimated with 90% confidence intervals obtained using Jeffrey's prior method.
Time frame: Up to 30 days post treatment
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