Clinical Trials /

Safety Study of ALRN-6924 in Patients With Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome

NCT02909972

Description:

Phase I, open label, multi-center dose escalation (DEP) and dose expansion (EXP) study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 in patients with acute myeloid leukemia or advanced myelodysplastic syndrome with wild-type (WT) TP53.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Unknown status

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of ALRN-6924 in Patients With Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome
  • Official Title: A Phase 1/1b Open-Label Study to Determine the Safety and Tolerability of ALRN-6924 Alone and in Combination With Cytarabine (Ara-C) in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome With Wild-Type TP53

Clinical Trial IDs

  • ORG STUDY ID: ALRN-6924-1-02
  • NCT ID: NCT02909972

Conditions

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
ALRN-6924ALRN-6924
ALRN-6924 in combination with cytarabineALRN-6924 in combination with Ara-CALRN-6924 in combination with cytarabine

Purpose

Phase I, open label, multi-center dose escalation (DEP) and dose expansion (EXP) study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 in patients with acute myeloid leukemia or advanced myelodysplastic syndrome with wild-type (WT) TP53.

Detailed Description

      Phase I, open label, multi-center dose escalation (DEP) and dose expansion (EXP) study
      designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and
      anti-tumor effects of ALRN-6924 in patients with acute myeloid leukemia or advanced
      myelodysplastic syndrome with wild-type (WT) TP53. ALRN-6924 is a stapled peptide designed to
      disrupt integration between the p53 tumor suppression protein and inhibition by murine double
      minute 2 (MDM2) and murine double minute X (MDMX).

      Men and women 18 years of age and older with relapsed or refractory acute myeloid leukemia or
      advanced myelodysplastic syndrome and for which standard treatment(s) are not available or
      are no longer effective can be enrolled. Treatment of patients in the DEP and EXP phases will
      continue in the study until documentation of disease progression, unacceptable toxicity, or
      patient or physician decision to discontinue study participation is made.
    

Trial Arms

NameTypeDescriptionInterventions
ALRN-6924ExperimentalFixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days
  • ALRN-6924
ALRN-6924 in combination with cytarabineExperimentalCytarabine (100 or 200 mg/m2) will be administered as an IV infusion followed by ALRN-6924 on Days 1, 8, and 15 every 28 days.
  • ALRN-6924 in combination with cytarabine

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female patients age 18 years and older, inclusive, at the time of informed
             consent

          -  Relapsed or refractory acute myeloid leukemia or IPSS-R intermediate/high/very
             high-risk MDS patients

          -  Wild-type TP53 status

          -  ECOG (Eastern Cooperative Oncology Group) performance status 0-2

          -  Predicted life expectancy of ≥3 months

          -  Adequate hematologic function

          -  Adequate hepatic function

          -  Acceptable coagulation profile

          -  Recovery from significant toxicities from previous therapies and sufficient time since
             last dose of previous therapy

          -  Negative serum or urine pregnancy test within 7 days prior to the first dose of
             ALRN-6924 for women of child-bearing potential

          -  Ability to understand and willingness to sign a written informed consent document

          -  Willing and able to undergo a pre- and subsequent on-treatment bone marrow biopsies

        Exclusion Criteria:

          -  Patients are eligible for available approved standard therapies

          -  Patients with a myelodysplastic/myeloproliferative neoplasm

          -  Previous treatment with investigational agents that inhibit MDM2 or MDMX activity
             (some MDM2-treated patients may be eligible)

          -  Patients with history of allogeneic stem cell transplantation

          -  Leukemic blast counts of >25,000/µl

          -  Deletion of chromosome 17, or del(17p)

          -  Patients with evidence of current central nervous system leukemic involvement

          -  Known hypersensitivity to any study drug component

          -  History of coagulopathy

          -  History of pulmonary embolism within 6 months prior to the first dose of ALRN-6924 or
             untreated DVT (deep vein thrombosis)

          -  Required concurrent use of anti-coagulants or anti-platelet medication, with the
             exception of aspirin doses ≤81 mg/day, low-dose SC heparin or SC low-molecular-weight
             heparin for DVT prophylaxis, or heparin flushes to maintain IV catheter patency

          -  Patients with pre-existing history of or known cardiovascular risk

          -  Clinically significant gastrointestinal bleeding within 6 months prior to the first
             dose of ALRN-6924

          -  Clinically significant third-space fluid accumulation

          -  Pregnant or lactating females

          -  Evidence of any serious and/or unstable pre-existing medical condition that would
             interfere with patient safety ability to provide informed consent

          -  Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C

          -  Known history of another primary malignancy that has not been in remission for ≥1 year

          -  Any other condition that may interfere with compliance of the study protocol

          -  Required use of medications predominantly cleared by hepatobiliary transporters within
             48 hours of study drug infusion
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:From first dose up to 30 days after last dose
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetics of ALRN-6924 and cytarabine: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame:8 days
Safety Issue:
Description:
Measure:Pharmacokinetics of ALRN-6924 and cytarabine: Maximum plasma concentration (Cmax)
Time Frame:8 days
Safety Issue:
Description:
Measure:Pharmacokinetics of ALRN-6924 and cytarabine: Area under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]
Time Frame:8 days
Safety Issue:
Description:
Measure:Pharmacokinetics of ALRN-6924: Half-life (t1/2)
Time Frame:8 days
Safety Issue:
Description:
Measure:Immunogenicity of ALRN-6924: induction of an immune response
Time Frame:From first dose day up to 30 days after last dose
Safety Issue:
Description:
Measure:Response as evaluated by International Working Group response criteria for MDS (Cheson 2006)
Time Frame:Two years
Safety Issue:
Description:
Measure:Response as evaluated by AML Response Criteria for AML (Dohner 2010)
Time Frame:Two years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aileron Therapeutics

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