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

NCT04207190

Last updated date
Study Location
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Contact
1-800-718-1021

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

By phone

Pfizer Clinical Trials Contact Center

1-800-718-1021

By email

Contact

[email protected]

Call Now

Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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, 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 tablets


- 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

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

TRY A NEW SEARCH

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.

Based on your search, you may also be interested in

Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid LeukemiaTalazoparib and Gemtuzumab Ozogamicin for the Treatment of CD33 Positive Relapsed or Refractory Acute Myeloid Leukemia
NCT04207190
  1. Buffalo, New York
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
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
  • Recurrent Acute Myeloid Leukemia
  • Refractory Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: Gemtuzumab Ozogamicin
    Given IV
    Other Names:
    • Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody
    • CDP-771
    • CMA-676
    • gemtuzumab
    • hP67.6-Calicheamicin
    • Mylotarg
    • WAY-CMA-676
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
  • Drug: Talazoparib
    Given PO
    Other Names:
    • BMN 673
    • BMN-673
  • Drug: Talazoparib Tosylate
    Given PO
    Other Name: Talzenna
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:
  • Drug: Gemtuzumab Ozogamicin
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
  • Drug: Talazoparib
  • Drug: Talazoparib Tosylate
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
 (submitted: December 18, 2019)
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:

  • 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

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, 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 tablets
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
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
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Eunice S WangRoswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP