NCT02909972

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
55

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Sep 2016

Typical duration for phase_1

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2016

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

September 9, 2016

Completed
12 days until next milestone

First Posted

Study publicly available on registry

September 21, 2016

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2019

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2019

Completed
Last Updated

November 19, 2019

Status Verified

November 1, 2019

Enrollment Period

2.6 years

First QC Date

September 9, 2016

Last Update Submit

November 18, 2019

Conditions

Acute Myeloid LeukemiaMyelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

  • 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

    From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)

  • 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

    From the first dose until the end of Cycle 2 (each cycle is 28 days)

Secondary Outcomes (6)

  • 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)

  • 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)

  • Determine immunogenicity of ALRN-6924

    Approximately 16 weeks

  • 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

  • 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

  • +1 more secondary outcomes

Study Arms (2)

ALRN-6924

EXPERIMENTAL

Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days

Drug: ALRN-6924

ALRN-6924 in combination with cytarabine

EXPERIMENTAL

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

Interventions

ALRN-6924DRUG

Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days.

ALRN-6924
ALRN-6924 in combination with cytarabineDRUG

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.

Also known as: ALRN-6924 in combination with Ara-C
ALRN-6924 in combination with cytarabine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Unknown Facility

Denver, Colorado, 80218, United States

Location

Unknown Facility

Tampa, Florida, 33612, United States

Location

Unknown Facility

The Bronx, New York, 10461, United States

Location

Unknown Facility

Portland, Oregon, 97239-3098, United States

Location

Unknown Facility

Greenville, South Carolina, 29605, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteMyelodysplastic Syndromes

Interventions

Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Diseases

Intervention Hierarchy (Ancestors)

CytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 9, 2016

First Posted

September 21, 2016

Study Start

September 1, 2016

Primary Completion

April 1, 2019

Study Completion

August 1, 2019

Last Updated

November 19, 2019

Record last verified: 2019-11

Data Sharing

IPD Sharing
Will not share

Locations

US(6)