Clinical trial NCT02909972: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Lead sponsor: Aileron Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-09-21
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Evaluate the safety and tolerability of ALRN-6924 alone and in combination with cytarabine
timeFrame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
measure: Determine maximum tolerated dose (MTD)
timeFrame: From the first dose until the end of Cycle 2 (each cycle is 28 days)
Secondary outcomes:
measure: Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
timeFrame: First 2 cycles (each cycle is 28 days)
measure: Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
timeFrame: First 2 cycles (each cycle is 28 days)
measure: Determine immunogenicity of ALRN-6924
timeFrame: Approximately 16 weeks
measure: 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
timeFrame: Approximately 16 weeks
measure: 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
timeFrame: Approximately 16 weeks
measure: 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
timeFrame: Approximately 16 weeks
Other outcomes:
Locations:
city: Denver
country: United States
state: Colorado
city: Tampa
country: United States
state: Florida
city: Bronx
country: United States
state: New York
city: Portland
country: United States
state: Oregon
city: Greenville
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
Study officials:
References: