Safety Study of ALRN-6924 in Patients With Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome
Primary Purpose
Acute Myeloid Leukemia, Myelodysplastic Syndromes
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ALRN-6924
ALRN-6924 in combination with cytarabine
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ALRN-6924
ALRN-6924 in combination with cytarabine
Arm Description
Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days
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.
Outcomes
Primary Outcome Measures
Evaluate the safety and tolerability of ALRN-6924 alone and in combination with cytarabine
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Determine maximum tolerated dose (MTD)
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
Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
Peak Plasma Concentration (Cmax)
Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
Area under the plasma concentration versus time curve [AUC]
Determine immunogenicity of ALRN-6924
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
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
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
International Working Group (IWG) Criteria for hematological improvement in MDS (Cheson et al, 2000)
Full Information
NCT ID
NCT02909972
First Posted
September 9, 2016
Last Updated
November 18, 2019
Sponsor
Aileron Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02909972
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
April 2019 (Actual)
Study Completion Date
August 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aileron Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ALRN-6924
Arm Type
Experimental
Arm Description
Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days
Arm Title
ALRN-6924 in combination with cytarabine
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
ALRN-6924
Intervention Description
Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days.
Intervention Type
Drug
Intervention Name(s)
ALRN-6924 in combination with cytarabine
Other Intervention Name(s)
ALRN-6924 in combination with Ara-C
Intervention Description
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.
Primary Outcome Measure Information:
Title
Evaluate the safety and tolerability of ALRN-6924 alone and in combination with cytarabine
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Time Frame
From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
Title
Determine maximum tolerated dose (MTD)
Description
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
Time Frame
From the first dose until the end of Cycle 2 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
Description
Peak Plasma Concentration (Cmax)
Time Frame
First 2 cycles (each cycle is 28 days)
Title
Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
Description
Area under the plasma concentration versus time curve [AUC]
Time Frame
First 2 cycles (each cycle is 28 days)
Title
Determine immunogenicity of ALRN-6924
Description
Incidence of anti-ALRN-6924 antibodies
Time Frame
Approximately 16 weeks
Title
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
Description
International Working Group (IWG) Criteria (Cheson et al, 2006)
Time Frame
Approximately 16 weeks
Title
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
Description
AML response criteria (Dohner et al, 2010)
Time Frame
Approximately 16 weeks
Title
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
Description
International Working Group (IWG) Criteria for hematological improvement in MDS (Cheson et al, 2000)
Time Frame
Approximately 16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239-3098
Country
United States
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety Study of ALRN-6924 in Patients With Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome
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