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

Phase 1

Completed

• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes
• Interventions: Drug: ALRN-6924; Drug: ALRN-6924 in combination with cytarabine

• Registration Number: NCT02909972
• Lead Sponsor: Aileron Therapeutics, Inc.

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 Timeline

• Study Start: 2016-09
• Study First Submitted: 2016-09-09
• Study First Submitted QC: 2016-09-19
• Study First Posted: 2016-09-21
• Primary Completion: 2019-04
• Study Completion: 2019-08
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-18
• Last Update Posted: 2019-11-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ALRN-6924	ALRN-6924	Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days
ALRN-6924 in combination with cytarabine	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 for hematological improvement in MDS (Cheson et al, 2000)