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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02909972
Recruitment Status : Completed
First Posted : September 21, 2016
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
Aileron Therapeutics

Tracking Information
First Submitted Date  ICMJE September 9, 2016
First Posted Date  ICMJE September 21, 2016
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE September 2016
Actual Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2019)
  • 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) ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
  • Determine maximum tolerated dose (MTD) [ Time Frame: From the first dose until the end of Cycle 2 (each cycle is 28 days) ]
    Determine the dose limiting toxicities (DLT) and the maximum tolerated dose (MTD) or the optimal biological dose (OBD) of ALRN-6924 in adult patients with AML or MDS
Original Primary Outcome Measures  ICMJE
 (submitted: September 19, 2016)
Maximum tolerated dose [ Time Frame: From first dose up to 30 days after last dose ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2019)
  • 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) ]
    Peak Plasma Concentration (Cmax)
  • 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) ]
    Area under the plasma concentration versus time curve [AUC]
  • Determine immunogenicity of ALRN-6924 [ Time Frame: Approximately 16 weeks ]
    Incidence of anti-ALRN-6924 antibodies
  • 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 ]
    International Working Group (IWG) Criteria (Cheson et al, 2006)
  • 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 ]
    AML response criteria (Dohner et al, 2010)
  • 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 ]
    International Working Group (IWG) Criteria for hematological improvement in MDS (Cheson et al, 2000)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2016)
  • Pharmacokinetics of ALRN-6924 and cytarabine: Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 8 days ]
  • Pharmacokinetics of ALRN-6924 and cytarabine: Maximum plasma concentration (Cmax) [ Time Frame: 8 days ]
  • Pharmacokinetics of ALRN-6924 and cytarabine: Area under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] [ Time Frame: 8 days ]
  • Pharmacokinetics of ALRN-6924: Half-life (t1/2) [ Time Frame: 8 days ]
  • Immunogenicity of ALRN-6924: induction of an immune response [ Time Frame: From first dose day up to 30 days after last dose ]
  • Response as evaluated by International Working Group response criteria for MDS (Cheson 2006) [ Time Frame: Two years ]
  • Response as evaluated by AML Response Criteria for AML (Dohner 2010) [ Time Frame: Two years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of ALRN-6924 in Patients With Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Intervention  ICMJE
  • Drug: ALRN-6924
    Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days.
  • Drug: ALRN-6924 in combination with cytarabine
    Cytarabine (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.
    Other Name: ALRN-6924 in combination with Ara-C
Study Arms  ICMJE
  • Experimental: ALRN-6924
    Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days
    Intervention: Drug: ALRN-6924
  • Experimental: ALRN-6924 in combination with cytarabine
    Cytarabine (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.
    Intervention: Drug: ALRN-6924 in combination with cytarabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 15, 2019)
55
Original Estimated Enrollment  ICMJE
 (submitted: September 19, 2016)
60
Actual Study Completion Date  ICMJE August 2019
Actual Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02909972
Other Study ID Numbers  ICMJE ALRN-6924-1-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Aileron Therapeutics
Study Sponsor  ICMJE Aileron Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Aileron Therapeutics
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP