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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

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

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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 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
Actual Study Start Date : September 2016
Actual Primary Completion Date : April 2019
Actual Study Completion Date : August 2019


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. 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

  2. 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


Secondary Outcome Measures :
  1. 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)

  2. 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]

  3. Determine immunogenicity of ALRN-6924 [ Time Frame: Approximately 16 weeks ]
    Incidence of anti-ALRN-6924 antibodies

  4. 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)

  5. 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)

  6. 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)



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:

  • 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

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


Locations
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United States, Colorado
Denver, Colorado, United States, 80218
United States, Florida
Tampa, Florida, United States, 33612
United States, New York
Bronx, New York, United States, 10461
United States, Oregon
Portland, Oregon, United States, 97239-3098
United States, South Carolina
Greenville, South Carolina, United States, 29605
United States, Tennessee
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Aileron Therapeutics
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Responsible Party: Aileron Therapeutics
ClinicalTrials.gov Identifier: NCT02909972    
Other Study ID Numbers: ALRN-6924-1-02
First Posted: September 21, 2016    Key Record Dates
Last Update Posted: November 19, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
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