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

NCT04207190 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: I 435819NCI-2019-07826
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 12 months post treatment

Secondary Outcomes (8)

• Complete remission rate

  Up to 12 months post treatment

• Best response rate

  Up to 12 months post treatment

• Duration of remission

  Up to 12 months post treatment

• Leukemia-free survival (LFS)

  Up to 12 months post treatment

• Transfusion independence rate

  Up to 12 months post treatment

Study Arms (1)

Treatment (talazoparib, gemtuzumab ozogamicin)

EXPERIMENTAL

Patients receive talazoparib PO daily on days 1-21 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.

Drug: Gemtuzumab Ozogamicin; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Talazoparib; Drug: Talazoparib Tosylate

Interventions

Gemtuzumab Ozogamicin DRUG

Given IV

Also known as: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676

Treatment (talazoparib, gemtuzumab ozogamicin)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (talazoparib, gemtuzumab ozogamicin)

Questionnaire Administration OTHER

Ancillary studies

Treatment (talazoparib, gemtuzumab ozogamicin)

Talazoparib DRUG

Given PO

Also known as: BMN 673, BMN-673

Treatment (talazoparib, gemtuzumab ozogamicin)

Talazoparib Tosylate DRUG

Given PO

Also known as: Talzenna

Treatment (talazoparib, gemtuzumab ozogamicin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group performance status between 0-1
• 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)
• Peripheral white blood cell (WBC) counts \<25,000/mcL. Patients are allowed to receive hydroxyurea and/or leukapheresis to control and maintain WBC count prior to enrollment and can continue on hydroxyurea through Cycle 1 Day 28 or until first disease assessment
• 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

You may not qualify if:

• 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:
• Severe cardiac disorder (symptomatic congestive heart failure requiring treatment, chronic unstable angina pectoris, myocardial infarction, cardiac arrhythmia, torsades de pointes,
• Neurologic impairment (cerebrovascular accident, transient ischemic attack)
• Severe pulmonary disorder (e.g. DLCO of 65% or less or a forced expiratory volume in 1 second \[FEV1\]) of 65% of less)
• Moderate hepatic impairment with total bilirubin \>1.5 x upper limit of normal (ULN),

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Pfizer: collaborator

Study Sites (2)

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Gemtuzumab; talazoparib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Eunice S Wang

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 20, 2019
• Study Start: October 23, 2020
• Primary Completion: May 26, 2024
• Study Completion: June 29, 2024
• Last Updated: November 1, 2024

Record last verified: 2024-10

Locations

US (2)