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

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ClinicalTrials.gov Identifier: NCT02909972
Recruitment Status : Recruiting
First Posted : September 21, 2016
Last Update Posted : June 27, 2017
Sponsor:
Information provided by (Responsible Party):
Aileron Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Drug: ALRN-6924 Drug: ALRN-6924 in combination with cytarabine Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : September 2016
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : April 2018


Arm Intervention/treatment
Experimental: ALRN-6924
Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days
Drug: ALRN-6924
Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days.

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.
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




Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: From first dose up to 30 days after last dose ]

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


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02909972


Contacts
Contact: Marie Payton mpayton@aileronrx.com

Locations
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Leyla Khavarian    813-745-6927    Leyla.Khavarian@Moffitt.org   
United States, New York
Montefiore Einstein Center for Cancer Care Recruiting
The Bronx, New York, United States, 10461
Contact: Apoorva Talanki    718-405-8545    atalanki@montefiore.org   
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Peter Blundell    503-494-6171    blundell@ohsu.edu   
United States, South Carolina
Institute for Translational Oncology Research (ITOR) Recruiting
Greenville, South Carolina, United States, 29605
Contact: Lisa Johnson    864-455-3600    ljohnson4@ghs.org   
Sponsors and Collaborators
Aileron Therapeutics
Investigators
Study Director: Dawn Pinchasik, MD Aileron Therapeutics

Responsible Party: Aileron Therapeutics
ClinicalTrials.gov Identifier: NCT02909972     History of Changes
Other Study ID Numbers: ALRN-6924-1-02
First Posted: September 21, 2016    Key Record Dates
Last Update Posted: June 27, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs