Overview

Talazoparib and Gemtuzumab Ozogamicin for the Treatment of CD33 Positive Relapsed or Refractory Acute Myeloid Leukemia

Status:
Recruiting
Trial end date:
2023-02-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Roswell Park Cancer Institute
Collaborators:
National Cancer Institute (NCI)
Pfizer
Treatments:
Calicheamicins
Gemtuzumab
Talazoparib
Criteria
Inclusion Criteria:

- 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 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

Exclusion Criteria:

- 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