What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents (HMAs) like azacitidine and decitabine, and combination therapies such as low-dose cytarabine (LoDAC) with venetoclax. Known side effects of these treatments include cytopenias (anemia, neutropenia, thrombocytopenia), febrile neutropenia, gastrointestinal symptoms (nausea, diarrhea), mucocutaneous ulcers, and potential for increased infection risk. Specific to PARP inhibitors like Talazoparib, common side effects include anemia, thrombocytopenia, neutropenia, nausea, anorexia, and asthenia. These side effects are generally manageable with dose modifications and supportive care.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML), including hypomethylating agents (HMAs) like azacitidine and decitabine. These agents are often used in combination with venetoclax, a BCL2 inhibitor, which has shown superior outcomes compared to HMA monotherapy. While the context does not mention specific FDA approvals for PARP inhibitors like Talazoparib in AML, it does highlight the use of HMAs and BCL2 inhibitors as effective treatment options.

What other types of research exist?

Promising novel alternatives to Talazoparib for AML patients include: 1) Hypomethylating agents (HMAs) such as Azacitidine and Decitabine, which have shown comparable efficacy and are well-tolerated. 2) Venetoclax, particularly in combination with low-dose cytarabine (LoDAC), which has demonstrated superior outcomes compared to LoDAC monotherapy. 3) IDH inhibitors like Ivosidenib (for IDH1 mutations) and Enasidenib (for IDH2 mutations), which target specific genetic mutations in AML. These alternatives offer different mechanisms of action and have shown promising results in clinical studies.

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Anti-metabolite

Talazoparib + Chemotherapy for Acute Myeloid Leukemia (PARPAML Trial)

Phase 1

Recruiting

Led By Jennifer L Kamens, MD

Research Sponsored by Stanford University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

PCR or NGS-based demonstration of leukemogenic lesion identical to diagnosis

Acute myeloid leukemia (AML) OR acute leukemia of ambiguous lineage (acute undifferentiated leukemia or mixed phenotype acute leukemia), specified as either refractory (persistent leukemia after at least 2 courses of induction chemotherapy) or relapsed, and further defined as any one of the criteria below:

Must not have

Patients receiving or planning to receive ANY concurrent cancer therapy, including chemotherapy, radiation therapy, immunotherapy or biologic therapy.

Female subjects with infants who do NOT agree to abstain from breastfeeding.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety of using talazoparib with standard chemotherapy in cancer patients. Talazoparib works by stopping cancer cells from repairing themselves, which could make chemotherapy more effective. The study aims to find the safest dose combination and see if this approach helps patients. Talazoparib is FDA approved for certain types of breast cancer that have spread and were previously treated with chemotherapy.

Who is the study for?

This trial is for children and young adults up to 21 years old with relapsed or refractory Acute Myeloid Leukemia (AML) or similar conditions. They should have had a stem cell transplant at least 60 days ago, be recovered from previous treatments, and not have uncontrolled infections or other cancer therapies ongoing. Pregnant individuals or those with certain leukemia subtypes are excluded.

What is being tested?

The study tests the safety and effectiveness of Talazoparib combined with chemotherapy drugs Gemcitabine and Topotecan in pediatric AML patients. It's a Phase 1 trial that will first find the highest dose patients can tolerate without severe side effects before assessing how well it works.

What are the potential side effects?

Possible side effects include reactions related to bone marrow suppression like fatigue, infection risk increase, bleeding problems, as well as nausea, vomiting, liver function changes, heart issues reflected in ejection fraction changes, and kidney function impairment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My leukemia has the same genetic features as when first diagnosed.

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My leukemia is either not responding to treatment or has come back.

Select...

My cancer's genetic makeup has not changed significantly since diagnosis.

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My cancer is showing signs of returning, as confirmed by two tests.

Select...

It has been over 60 days since my stem cell transplant.

Select...

I had a stem cell transplant, have no active GVHD, and haven't taken calcineurin inhibitors for 4 weeks.

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My liver enzymes are within 5 times the normal limit.

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My bilirubin levels are within twice the normal range for my age.

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I can do most activities but may need help.

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I am 21 years old or younger.

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My cancer's genetic test shows the same abnormality as when first diagnosed.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am currently undergoing or planning to start any cancer treatment soon.

Select...

I agree not to breastfeed during the trial.

Select...

I have been diagnosed with APL or JMML.

Select...

I have been diagnosed with Bone Marrow Failure Syndrome.

Select...

I do not have any uncontrolled infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose limiting toxicity (DLT).

Secondary study objectives

Objective Response (OR)

Side effects data

From 2018 Phase 1 & 2 trial • 40 Patients • NCT02116777

100%

Fatigue

100%

Headache

67%

Platelet count decreased

67%

Hyperglycemia

67%

Anemia

67%

Back pain

33%

Weight loss

33%

Nausea

33%

Sinus tachycardia

33%

Investigations - Other, BUN DECREASED

33%

Urinary incontinence

33%

Peripheral motor neuropathy

33%

Hyponatremia

33%

Hypoglycemia

33%

Hypothyroidism

33%

Neutrophil count decreased

33%

White blood cell decreased

33%

Scoliosis

33%

Hypokalemia

33%

Insomnia

33%

Creatinine increased

33%

Alanine aminotransferase increased

33%

Peripheral sensory neuropathy

33%

Fever

33%

Diarrhea

33%

Hypermagnesemia

33%

Lymphocyte count decreased

33%

Hypophosphatemia

33%

Gastroesophageal reflux disease

33%

Skin ulceration

33%

Nervous system disorders - Other, PARALYSIS

33%

Muscle weakness lower limb

33%

Cough

33%

Non-cardiac chest pain

33%

Skin infection

33%

Nystagmus

33%

Arthralgia

33%

Gait disturbance

33%

Edema limbs

33%

Hypertension

33%

Investigations - Other, ALT DECREASED

33%

Chills

33%

Investigations - Other, AST DECREASED

33%

Nervous system disorders - Other, HYPOTONIC

33%

Alopecia

33%

Aspartate aminotransferase increased

33%

Blurred vision

33%

Constipation

33%

Pain in extremity

33%

Alkaline phosphatase increased

33%

Neuralgia

33%

Skin and subcutaneous tissue disorders - Other, LEFT LOWER LEG ERYTHEMA

33%

Anorexia

100%

80%

60%

40%

20%

Study treatment Arm

400 mcg/m²/Dose BMN 673 QD+20mg/m²/Dose TEM,Max 800 mcg/Day

600 mcg/m²/doseBMN 673 BID+55mg/m²/Dose TEM, Max 1000 mcg/Day

600 mcg/m²/Dose BMN 673 BID+30mg/m²/Dose TEM,Max 1000 mcg/Day

400 mcg/m²/Dose BMN 673 BID+20mg/m²/Dose TEM,Max 800 mcg/Day

600 mcg/m²/Dose BMN 673 BID+20mg/m²/Dose TEM,Max 1000 mcg/Day

600 mcg/m²/Dose BMN 673 BID+30mg/m²/Dose TEM, Max 1000 mcg/Day

600 mcg/m²/Dose BMN 673 BID+40mg/m²/Dose TEM, Max 1000 mcg/Day

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Talazoparib with topotecan and gemcitabineExperimental Treatment3 Interventions

Talazoparib will be administered orally on Days 1 to 5 concurrently with topotecan and a single dose of gemcitabine on Day 1 of 28 day cycle for 1 or 2 cycles. Subjects on dose level 5 will receive an additional 5 day treatment course of talazoparib on days 15-19.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Talazoparib

2021

Completed Phase 2

~2810

Gemcitabine

2017

Completed Phase 3

~1920

Topotecan

2017

Completed Phase 3

~2890

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Acute Myeloid Leukemia (AML) include chemotherapy, targeted therapy, and hypomethylating agents. Chemotherapy, such as cytarabine and daunorubicin, works by killing rapidly dividing cancer cells. Targeted therapies, like FLT3 inhibitors (e.g., gilteritinib) and IDH inhibitors (e.g., ivosidenib), specifically target genetic mutations in AML cells, thereby inhibiting their growth and survival. Hypomethylating agents, such as azacitidine and decitabine, work by reactivating tumor suppressor genes through DNA demethylation. PARP inhibitors like Talazoparib, although primarily studied in other cancers, target DNA repair mechanisms, making cancer cells more susceptible to damage. These treatments are crucial for AML patients as they offer personalized and potentially more effective options, improving outcomes and reducing side effects compared to traditional chemotherapy.

Molecular targeting in acute myeloid leukemia.Development of Personalized Molecular Therapy for Acute Myeloid Leukemia.Childhood acute myeloid leukaemia.