Clinical Trials /

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

NCT02909972

Description:

Phase 1/1b, open label, multi-center dose escalation and dose expansion study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 alone or in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia or advanced myelodysplastic syndrome with wild-type (WT) TP53

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

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02909972

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 1/1b, open label, multi-center dose escalation and dose expansion study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 alone or in combination with cytarabine in patients with relapsed/refractory 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 stabilized cell-permeating
      peptide designed to disrupt interaction between the p53 tumor suppression protein and its
      endogenous inhibitors 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:

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

          -  Confirmed or anticipated wild-type TP53

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

          -  Adequate hepatic and renal function

          -  Acceptable coagulation function

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

          -  Sufficient wash out from prior therapies and recovery from all significant toxicities

        Exclusion Criteria:

          -  Patients are eligible for available approved standard therapies

          -  Prior treatment with MDM2 inhibitor, with protocol specified exceptions

          -  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

          -  Prior specified cardiovascular risk factors

          -  Clinically significant gastrointestinal bleeding within 6 months

          -  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

          -  Second malignancy within one year, with protocol specified exceptions
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluate the safety and tolerability of ALRN-6924 alone and in combination with cytarabine
Time Frame:From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0

Secondary Outcome Measures

Measure:Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
Time Frame:First 2 cycles (each cycle is 28 days)
Safety Issue:
Description:Peak Plasma Concentration (Cmax)
Measure:Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
Time Frame:First 2 cycles (each cycle is 28 days)
Safety Issue:
Description:Area under the plasma concentration versus time curve [AUC]
Measure:Determine immunogenicity of ALRN-6924
Time Frame:Approximately 16 weeks
Safety Issue:
Description:Incidence of anti-ALRN-6924 antibodies
Measure:Determine best overall response, duration of response, morphologic leukemia-free state, leukemia free survival, percentage of MDA patients who have achieved hematologic improvement, changes in transfusion rate and early death rate
Time Frame:Approximately 16 weeks
Safety Issue:
Description:International Working Group (IWG) Criteria (Cheson et al, 2006)
Measure:Determine best overall response, duration of response, morphologic leukemia-free state, leukemia free survival, percentage of MDA patients who have achieved hematologic improvement, changes in transfusion rate and early death rate
Time Frame:Approximately 16 weeks
Safety Issue:
Description:AML response criteria (Dohner et al, 2010)
Measure:Determine best overall response, duration of response, morphologic leukemia-free state, leukemia free survival, percentage of MDA patients who have achieved hematologic improvement, changes in transfusion rate and early death rate
Time Frame:Approximately 16 weeks
Safety Issue:
Description:International Working Group (IWG) Criteria for hematological improvement in MDS (Cheson et al, 2000)

Details

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

Last Updated

November 19, 2019