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Recurrent Acute Myeloid LeukemiaPhase 1NCT04207190

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

A Phase 1 study testing Gemtuzumab Ozogamicin, Quality-of-Life Assessment and Questionnaire Administration in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Roswell Park Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gemtuzumab Ozogamicin, Quality-of-Life Assessment and Questionnaire Administration
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
2 sitesUnited States
Study dates
23 Oct 2020to 29 Jun 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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),
  • Eastern Cooperative Oncology (ECOG ) Performance Status ≥ 2,
  • Any other 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: Phase 1/1b Trial of Talazoparib and Gemtuzumab Ozogamicin in Adult Patients With Relapsed and/or Refractory Acute Myeloid Leukemia

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Gemtuzumab Ozogamicin, Quality-of-Life Assessment, Questionnaire Administration, Talazoparib, Talazoparib Tosylate
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gemtuzumab OzogamicinDrug

    Also called Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • TalazoparibDrug

    Also called BMN 673, BMN-673

    Given PO

  • Talazoparib TosylateDrug

    Also called Talzenna

    Given PO

Study groups in NCT04207190
Study groupRoleWhat they receive
Treatment (talazoparib, gemtuzumab ozogamicin)ExperimentalPatients 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.
Receives: Drug: Gemtuzumab Ozogamicin; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Talazoparib; Drug: Talazoparib Tosylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 28 days

  2. 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.

    Measured: Up to 12 months post treatment

Secondary outcomes (8)

  1. Complete remission rate

    The complete remission will be estimated with 90% confidence intervals obtained by Jeffrey's prior method.

    Measured: Up to 12 months post treatment

  2. Best response rate

    Best response rate will consist of CRi and partial remission (PR).

    Measured: Up to 12 months post treatment

  3. 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.

    Measured: Up to 12 months post treatment

  4. 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.

    Measured: Up to 12 months post treatment

  5. Transfusion independence rate

    Transfusion independence rate will be estimated with 90% confidence intervals obtained by Jeffrey's prior method.

    Measured: Up to 12 months post treatment

  6. Hematopoietic stem cell transplantation (HSCT) rates

    HSCT will be estimated with 90% confidence intervals obtained by Jeffrey's prior method.

    Measured: Up to 12 months post treatment

  7. Overall survival (OS)

    OS will be estimated using standard Kaplan-Meier methods, where estimates of the median will be obtained with 90% confidence intervals.

    Measured: Up to 12 months post treatment

  8. 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.

    Measured: Up to 30 days post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2019
  2. Study start23 Oct 2020
  3. Primary completion26 May 2024
  4. Study completion29 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04207190
Sponsor's protocol ID
I 435819
Other IDs
NCI-2019-07826, I 435819
Status last verified
Oct 2024
First submitted
10 Dec 2019
Last updated
1 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Gemtuzumab Ozogamicin, Quality-of-Life Assessment and Questionnaire Administration in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Roswell Park Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04207190.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2024.

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