Talazoparib and Gemtuzumab Ozogamicin for the Treatment of CD33 Positive Relapsed or Refractory Acute Myeloid Leukemia
NCT04207190
ABOUT THIS STUDY
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- Eastern Cooperative Oncology Group performance status between 0-2
- Creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance (Cockcroft and Gault ) > 30 mL/min (performed on plasma unless otherwise indicated)
- Alanine aminotransferase (ALT) =< 2.5 x ULN (performed on plasma unless otherwise indicated)
- Direct bilirubin < 1.5 mg/dL (performed on plasma unless otherwise indicated)
- Left ventricular ejection fraction (LVEF) >= 40% as assessed by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan performed within 28 days of enrollment
- Diagnosis of CD33+ acute myeloid leukemia (AML) with evidence of >= 5% myeloblasts in the bone marrow, peripheral blood, or in an extramedullary site by pathology. Any CD33 receptor expression level > 0.01% by institute flow cytometric analysis will suffice
- Relapsed or refractory disease, defined as:
- Any bone marrow relapse after allogeneic HSCT: subjects must be at least 1 month from HSCT at the time of screening and off immunosuppressive medication for at least 2 weeks at time of initial treatment (with the exception of low-dose steroids =< 20 mg prednisone equivalent) and have no active graft versus (vs.) host disease (GVHD)
- AML with no prior CR/CRi after at least 1 prior cycle of remission induction chemotherapy (i.e. cytarabine or hypomethylating based regimen(s) allowed)
- AML recurring after prior CR/CRi, which was achieved following at least one prior chemotherapy cycle (i.e. cytarabine or hypomethylating based regimen(s) allowed)
- Participants of childbearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
- Acute promyelocytic leukemia (APL, FAB M3) with t(15-17) and/or evidence of
promyelocytic leukemia/retinoic acid receptor alpha (PML-RAR alpha)
- Blast phase of prior chronic phase chronic myeloid leukemia with t(9;22)
- Receipt of chemotherapy (except for hydroxyurea), radiotherapy, or investigational
drug therapy within 2 weeks prior to treatment on study or those who have not
recovered from adverse events due to agents administered > 2 weeks earlier
- Known active central nervous system involvement; patients who have a history of
central nervous system (CNS) disease which has been effectively treated as defined by
at least one negative cerebrospinal sample prior to screening are eligible
- Active uncontrolled malignancy requiring ongoing chemotherapy and/or radiation.
Examples of eligible patients include individuals with a prior history of malignancy
treated with curative intent with no current evidence of active disease such as:
- Subjects with stage I breast cancer that has been completely and successfully
treated, requiring no therapy or only anti-hormonal therapy
- Subjects with T1N0M0 or T2N0M0 colorectal cancer who have been completely and
successfully resected and who are disease-free for > 2 years prior to screening
- Subjects with indolent prostate cancer, defined as clinical stage T1 or T2a,
Gleason score =< 6, and prostate specific antigen (PSA) < 10 ng/mL, requiring no
therapy or only anti-hormonal therapy
- Subjects with a history of basal cell or squamous cell carcinoma of the skin, or
carcinoma in situ of the cervix, fully resected, and with no evidence of active
disease
- Other prior or concurrent malignancies will be considered on a case-by-case basis
after discussion with the principal investigator (PI)
- Uncontrolled current medical illness including, but not limited to, symptomatic
congestive heart failure, unstable angina pectoris, myocardial infarction, cardiac
arrhythmia, torsades de pointes, cerebrovascular accident, transient ischemic attack,
or psychiatric illness/social situations that in the opinion of the investigator would
limit compliance with study requirements
- Known malabsorption syndrome or other condition that may impair the absorption of the
study drug and/or inability and/or unwillingness to swallow capsules
- Uncontrolled active systemic fungal, bacterial, viral, or other infection with patient
still exhibiting ongoing signs and symptoms due to infection despite appropriate
anti-infective therapy at time of screening
- Pregnant or breastfeeding female participants
- Known active hepatitis B, active hepatitis C, or any human immunodeficiency virus
(HIV) infection at the time of screening which requires therapy
- Presence of grade II-IV acute or extensive chronic GVHD at time of screening
- Unwilling or unable to follow protocol requirements
- Any condition which in the investigator's opinion deems the participant an unsuitable
candidate to receive study drug including, but not limited to, medical, psychological,
familial, social or geographical considerations
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Descriptive Information | |||||||
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Brief Title ICMJE | Talazoparib and Gemtuzumab Ozogamicin for the Treatment of CD33 Positive Relapsed or Refractory Acute Myeloid Leukemia | ||||||
Official Title ICMJE | Phase 1/1b Trial of Talazoparib and Gemtuzumab Ozogamicin in Adult Patients With Relapsed and/or Refractory Acute Myeloid Leukemia | ||||||
Brief Summary | 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. | ||||||
Detailed Description | 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 1-28 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 ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 Phase 2 | ||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment | ||||||
Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (talazoparib, gemtuzumab ozogamicin)
Patients receive talazoparib PO daily on days 1-28 and gemtuzumab ozogamicin 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. Interventions:
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. | |||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE | 20 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | February 1, 2023 | ||||||
Estimated Primary Completion Date | February 1, 2022 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | |||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04207190 | ||||||
Other Study ID Numbers ICMJE | I 435819 NCI-2019-07826 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) I 435819 ( Other Identifier: Roswell Park Cancer Institute ) | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||
Responsible Party | Roswell Park Cancer Institute | ||||||
Study Sponsor ICMJE | Roswell Park Cancer Institute | ||||||
Collaborators ICMJE | Pfizer | ||||||
Investigators ICMJE |
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PRS Account | Roswell Park Cancer Institute | ||||||
Verification Date | December 2020 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |