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

Sponsor

Aileron Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02909972

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

9.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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

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.

Study Design

Study Type:

Interventional

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 :

Sep 1, 2016

Actual Primary Completion Date :

Apr 1, 2019

Actual Study Completion Date :

Aug 1, 2019

Arms and Interventions

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 Names: ALRN-6924 in combination with Ara-C

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 Names:

ALRN-6924 in combination with Ara-C

Outcome Measures

Primary Outcome Measures

Evaluate the safety and tolerability of ALRN-6924 alone and in combination with cytarabine [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) [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

Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS) [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) [First 2 cycles (each cycle is 28 days)]
Area under the plasma concentration versus time curve [AUC]
Determine immunogenicity of ALRN-6924 [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 [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 [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 [Approximately 16 weeks]
International Working Group (IWG) Criteria for hematological improvement in MDS (Cheson et al, 2000)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Denver	Colorado	United States	80218
2	Tampa	Florida	United States	33612
3	Bronx	New York	United States	10461
4	Portland	Oregon	United States	97239-3098
5	Greenville	South Carolina	United States	29605
6	Nashville	Tennessee	United States	37203