talazoparib for Acute Myeloid Leukemia (AML)

Phase-Based Estimates
1
Effectiveness
1
Safety
University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD
talazoparib - Drug
Eligibility
18+
All Sexes
Eligible conditions
Acute Myeloid Leukemia (AML)

Study Summary

This study is evaluating the best dose of a new chemotherapy drug to use when it is given with a drug that is already in use to treat AML.

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Treatment Effectiveness

Effectiveness Estimate

1 of 3

Study Objectives

This trial is evaluating whether talazoparib will improve 3 primary outcomes in patients with Acute Myeloid Leukemia (AML). Measurement will happen over the course of Cycle length = 28 days.

Day 28
Phase 1 - Dose Finding
Phase 1 - Dose finding
Year 1
Phase 2 - Efficacy

Trial Safety

Safety Estimate

1 of 3

Trial Design

5 Treatment Groups

Phase 2 Arm C
Phase 2: Decitabine and Talazoparib Combo

This trial requires 25 total participants across 5 different treatment groups

This trial involves 5 different treatments. Talazoparib is the primary treatment being studied. Participants will be divided into 2 treatment groups. There is no placebo group. The treatments being tested are in Phase 1 & 2 and have already been tested with other people.

Phase 2: Decitabine and Talazoparib ComboPhase 2: Recommended Phase 2 Dose (RP2D) The MTD of the combination of decitabine with a dose of talazoparib of at least 0.25 mg is defined as the maximal tolerated dose of decitabine studied - and for that dose level, combined with the maximum dose of talazoparib for which the incidence of DLT was less than 33% in 6 participants treated and this will be chosen as the recommended Phase 2 dose (RP2D). Among potential combined dose levels at MTD, available pharmacodynamic data (PARP trapping) will also be considered in the choice of RP2D, as will any significant indications of differences in clinical efficacy
Phase 1: Decitabine and Talazoparib ComboPhase 1: Decitabine by IV daily for 5 days every 28 days. Talazoparib orally daily days 1-28. The 'outer layer' of this nested dose escalation trial will escalate the dose of the two drugs by sequentially going through dose levels 1-6 in the table found in the protocol. The standard algorithm of the 3+3 design will be applied.
Phase 2 Arm CAdult patients previously treated with a DNA methyltransferase inhibitor (decitabine, azacitidine or guadecitabine)
Phase 2 Arm AAdult patients with AML who are thought not to be likely to tolerate or respond to standard chemotherapy
Phase 2 Arm BAdult patients with AML that has not responded to previous treatment or has come back after responding to previous treatment
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Talazoparib
FDA approved
Decitabine
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: evaluated every 28 days through study completion, an average of 1 year.
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly evaluated every 28 days through study completion, an average of 1 year. for reporting.

Who is running the study

Principal Investigator
M. B.
Maria Baer, Principal Investigator
University of Maryland, Baltimore

Closest Location

University of Maryland Greenebaum Comprehensive Cancer Center - Baltimore, MD

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. You must have received newly diagnosed for Acute Myeloid Leukemia (AML). There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Diagnosis of AML based on 2008 WHO criteria. AML may be de novo, following a prior hematologic disorder, including MDS or Philadelphia chromosome-negative myeloproliferative neoplasm, and/or therapy-related.
Patients who have undergone autologous stem cell transplantation (autoSCT) are eligible provided that they are ≥ 4 weeks from stem cell infusion.
Age ≥18 years. Because no dosing or adverse event data are currently available on the use of decitabine or talazoparib in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
ECOG performance status ≤2 (Karnofsky ≥60%).
PHASE 2 ONLY: Patients previously untreated for AML who are considered unfit for cytotoxic chemotherapy by virtue of performance status, comorbidities, advanced age and/or low likelihood of response based on disease characteristics, or who decline cytotoxic induction chemotherapy.
PHASES 1 AND 2: Patients with AML that has relapsed after, or is refractory to, first-line therapy, with or without subsequent additional therapy, and are currently considered unfit for, or unlikely to respond to, cytotoxic chemotherapy.
Patients who have undergone allogeneic SCT (alloSCT) are eligible if they are ≥ 60 days from stem cell infusion, have no evidence of graft versus host disease (GVHD) > Grade 1, and are ≥ 2 weeks off all immunosuppressive therapy.
Previous cytotoxic chemotherapy must have been completed at least 3 weeks and radiotherapy at least 2 weeks prior to Day 1 of treatment on the study, and all adverse events (excluding alopecia) due to agents administered more than 4 weeks earlier should have recovered to < Grade 1. Patients with hematologic malignancies are expected to have hematologic abnormalities at study entry. Hematologic abnormalities that are thought to be primarily related to leukemia are not considered to be toxicities (AE) and do not need to resolve to < Grade 1.
Prior DNA methyl transferase inhibitor administration (azacitidine, decitabine, or guadecitabine) for AML or for antecedent MDS is allowed if this clinical trial is considered the best treatment option, but azacitidine, decitabine, or guadecitabine must have been stopped at least 3 weeks prior to Day 1 of treatment on the study.
All biologic agents including hematopoietic growth factors must have been stopped at least 1 week prior to Day 1 of treatment on the study.

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What are the signs of acute myeloid leukemia (aml)?

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The signs of acute myeloid leukemia (aml) were also shown. You should start getting familiarized with the signs for acute myeloid leukemia (aml) that could become an important first step in learning how to diagnose AML. It will help you get the proper treatment for a patient when needed.

Unverified Answer

What causes acute myeloid leukemia (aml)?

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Many studies have linked the development of AML with congenital heart disease and maternal and paternal exposures to certain chemicals or ionizing radiation. Genetic risk factors involved in AML are thought to be independent of exposure to chemical agents or ionizing radiation, but, at this time, the magnitude of their respective contributions remains unclear.

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What are common treatments for acute myeloid leukemia (aml)?

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The most common treatments for [acute lymphoblastic leukemia](https://www.withpower.com/clinical-trials/acute-lymphoblastic-leukemia) (alpBL) are chemotherapy and supportive therapy and for acute myeloid leukemia (alpAML) supportive care with chemotherapy is the only common treatment.

Unverified Answer

How many people get acute myeloid leukemia (aml) a year in the United States?

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The American Cancer Society estimates that the number of new cases of acute lymphocytic and myeloid leukemias as well as acute leukemias in general will roughly double between 1992 and 2012.

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Can acute myeloid leukemia (aml) be cured?

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In the majority of patients, the remission is not maintained. However, patients will sometimes respond to a second, lower-intensity, course of therapy. Patients who do fail to remit on a given course of therapy can usually achieve complete remission with other, higher-intensity courses. In such patients, long-term survival can be expected.

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What is acute myeloid leukemia (aml)?

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AML is a type of cancers, of which most are caused by a genetic mutation in their DNA. AML accounts for 3/4 of all leukemias in children and is the leading cause of [treatment failure in AML patients] (https://medicalmisdiagnosis.info/acute-myeloid-leukemia.html and https://www.medmars.org/Cancer/Leukaemia/Bone-marrow/ Acute Myeloid Leukaemia).

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Does acute myeloid leukemia (aml) run in families?

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Despite the recent evidence for a role for genetic factors in acute myeloid leukemia (aml), all families showed some signs of disease, suggesting that genetic factors are probably not the sole cause and underscore the need for additional studies.

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Has talazoparib proven to be more effective than a placebo?

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Talazoparib improved survival relative to a placebo in patients with de novo AML who did not achieve the best response upon initial therapy. These data suggest talazoparib may have an additional role in AML in addition to its proven role in solid tumors.

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Have there been other clinical trials involving talazoparib?

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This trial met all required standards and safety data were reported with the publication. Talazoparib is an effective anti-cancer agent that deserves further exploration in patients with a B-cell malignancy.

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Who should consider clinical trials for acute myeloid leukemia (aml)?

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For young adults with high grade MDS who are able to tolerate long-term chemotherapy or for patients with intermediate to high-risk MDS whose treatment failure causes substantial disease-related morbidity, these groups might be appropriate for treatment on randomized trial, if they have not yet been studied in a clinical trial.

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How does talazoparib work?

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As a single-agent, talazoparib causes apoptosis in AML blasts in a fashion similar to bortezomib, but with a shorter drug-free cytotoxic effect. The use of tPX 3 cycles seems feasible, but further study is needed to determine the optimal dosing schedules and to confirm its efficacy as a single agent.

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Have there been any new discoveries for treating acute myeloid leukemia (aml)?

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There have been some new treatments that have been developed to treat aml; as the disease has progressed, more research has been done to produce more effective treatments. It is difficult to treat all aml patients because the disease often recurs, and it is also difficult to find a cure. Researchers are currently developing various new treatments to treat patients with leukemias. There has been some progress in getting to a treatment that could be effective for many people with leukemia, but many others are still going to need treatment for this type of cancer. In this section of the magazine, you will see new treatments for people who have struggled with aml during the past months and you will get to see how hard it has been to treat the disease.

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See if you qualify for this trial
Get access to this novel treatment for Acute Myeloid Leukemia (AML) by sharing your contact details with the study coordinator.