Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

APR-246 & Azacitidine for the Treatment of TP53 Mutant Myelodysplastic Syndromes (MDS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03745716
Recruitment Status : Active, not recruiting
First Posted : November 19, 2018
Last Update Posted : July 29, 2021
Sponsor:
Information provided by (Responsible Party):
Aprea Therapeutics

Tracking Information
First Submitted Date  ICMJE November 14, 2018
First Posted Date  ICMJE November 19, 2018
Last Update Posted Date July 29, 2021
Actual Study Start Date  ICMJE January 11, 2019
Actual Primary Completion Date November 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2018)
To compare the complete response rate (CR) with APR 246 + azacitidine treatment vs. azacitidine only. [ Time Frame: Through study completion, an average of 1 year ]
To compare the complete response rate, defined as the proportion of patients who achieve complete remission (CR), and duration of CR with APR 246 + azacitidine treatment vs. azacitidine only.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE APR-246 & Azacitidine for the Treatment of TP53 Mutant Myelodysplastic Syndromes (MDS)
Official Title  ICMJE A Phase III Multicenter, Randomized, Open Label Study of APR-246 in Combination With Azacitidine Versus Azacitidine Alone for the Treatment of (Tumor Protein) TP53 Mutant Myelodysplastic Syndromes
Brief Summary A Phase III, multicenter, randomized study to compare the rate of complete response (CR) and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.
Detailed Description

A Phase III, multicenter, randomized study to compare the rate of CR and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.

Treatment will be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's disease.

Patients will be randomized (1:1) to one of two arms:

  1. Experimental arm: APR-246 + azacitidine; or
  2. Control arm: Azacitidine
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This will be a Phase III, multicenter, randomized study to compare the rate of CR and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.

Treatment will be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's disease.

Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65):

  • Experimental arm: APR-246 + azacitidine; or
  • Control arm: Azacitidine
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE MDS
Intervention  ICMJE
  • Drug: APR-246 + azacitidine

    Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65):

    Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine

  • Drug: Azacitidine

    Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65):

    Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine

Study Arms  ICMJE
  • Experimental: Experimental arm: APR-246 + azacitidine
    Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65):
    Intervention: Drug: APR-246 + azacitidine
  • Experimental: Control arm: Azacitidine
    Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65):
    Intervention: Drug: Azacitidine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 3, 2020)
154
Original Estimated Enrollment  ICMJE
 (submitted: November 16, 2018)
156
Estimated Study Completion Date  ICMJE December 2021
Actual Primary Completion Date November 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed Informed Consent (ICF) and is able to comply with protocol requirements
  • Documented diagnosis of MDS, according to World Health Organization (WHO) classification
  • Patient has adequate organ function as defined by the following laboratory values:

    1. Creatinine clearance > 30 mL/min (by Cockcroft-Gault method)
    2. Total serum bilirubin < 1.5 x Upper Limit of Normal (ULN) or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's Syndrome or hemolysis or who required regular blood transfusions
    3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN
  • Age ≥18 years at the time of signing the informed consent form (ICF)
  • Having at least one TP53 mutation which is not benign or likely benign
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • If of childbearing potential, negative pre-treatment urine or serum pregnancy test
  • If of childbearing potential (males and females), willing to use an effective form of contraception such as latex condom, hormonal birth control, intrauterine device or double barrier method during chemotherapy treatment and for at least six months thereafter

Exclusion Criteria:

  • Patient has a known history of human immunodeficiency virus (HIV) or active hepatitis B or active hepatitis C infection (testing not mandatory)
  • Patient has any of the following cardiac abnormalities (as determined by treating MD):

    1. Myocardial infarct within six months prior to registration,
    2. New York Heart Association Class II or worse heart failure (Appendix II) or known left ventricular ejection fraction (LVEF) < the institution lower limit of normal as assessed by echocardiogram
    3. A history of familial long QT syndrome,
    4. Clinically significant pericardial disease
    5. Electrocardiographic evidence of acute ischemia
    6. Symptomatic atrial or ventricular arrhythmias not controlled by medications
    7. QTc ≥ 470 msec (QT cardiac interval)
    8. Bradycardia (<40 bpm)
  • Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Patients with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g. cervix) may enroll irrespective of the time of diagnosis
  • Prior exposure to azacitidine, decitabine or investigational hypomethylating agent
  • Prior exposure to intensive chemotherapy
  • Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS within 14 days of the first day of study drug treatment
  • No concurrent use of erythroid stimulating agents
  • Patients with history of allogeneic stem cell transplantation
  • Pregnant women are excluded from this study because APR-246 has not been studied in pregnant patients. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with APR 246, breastfeeding should be discontinued if the mother is treated with APR-246.
  • Patients with active uncontrolled infections
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03745716
Other Study ID Numbers  ICMJE A-18-15331
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aprea Therapeutics
Study Sponsor  ICMJE Aprea Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David Sallman, MD, PhD Moffitt Cancer Center, Tampa, US
PRS Account Aprea Therapeutics
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP