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APR-246 in Combination With Azacitidine for TP53 Mutated AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes) Following Allogeneic Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT03931291
Recruitment Status : Recruiting
First Posted : April 30, 2019
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Aprea Therapeutics AB

Brief Summary:
A multi-center, open label, Phase II clinical trial to assess the safety and efficacy of APR-246 in combination with azacitidine as maintenance therapy after allogeneic HSCT (hematopoietic stem cell transplant) for patients with TP53 mutant AML or MDS.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia or Myelodysplastic Syndromes Drug: APR-246 Phase 2

Detailed Description:

A multi-center, open label, Phase II clinical trial to assess the safety and efficacy of APR-246 in combination with azacitidine as maintenance therapy after allogeneic HSCT for patients with TP53 mutant AML or MDS.

Patients will be prescreened for TP53 mutant AML or MDS before they have a HSCT. In order to proceed with APR-246 and azacitidine treatment, engraftment must be confirmed between Day 30 to Day 100 post-HSCT.

APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 31 participants
Intervention Model: Single Group Assignment
Intervention Model Description: APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of APR-246 in Combination With Azacitidine as Maintenance Therapy for TP53 Mutated AML or MDS Following Allogeneic Stem Cell Transplant
Actual Study Start Date : September 16, 2019
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : September 30, 2021


Arm Intervention/treatment
Experimental: Experimental arm: APR-246 + azacitidine
APR-246 and azacitidine maintenance therapy will continue for a maximum of 12 cycles
Drug: APR-246
APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.
Other Name: Azacitidine




Primary Outcome Measures :
  1. To assess relapse-free survival (RFS) in patients with TP53 mutated AML or MDS after undergoing allogeneic hematopoietic stem cell transplant (HSCT). [ Time Frame: Through study completion, an average of 1 year ]
    Relapse-free survival (RFS) at 12 months 2. To evaluate the safety and tolerability of APR-246 in combination with azacitidine as maintenance treatment post-HSCT.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient must have previously met pre-transplantation eligibility.
  2. Patient has received an allogeneic transplant for AML or MDS.
  3. Any standard (non-study) conditioning [MAC (myeloablative conditioning), RIC (reduced intensity conditioning), or NMA (non-myeloablative conditioning)] will be permitted.
  4. Patient is ≥ 30 days and ≤ 100 days from hematopoietic cell infusion.
  5. Patient is in complete remission after the transplant and has achieved engraftment. .
  6. Patients who have developed grades II-IV acute GVHD (graft versus host disease) will be allowed to initiate maintenance therapy based on the following criteria:
  7. Females must either:

    Be of non-childbearing potential postmenopausal (defined as at least 1 year without menses) prior to screening, or documented as surgically sterilized (e.g., hysterectomy or tubal ligation) at least 1 month prior to the screening visit Or, if of childbearing potential, Agree not to try to become pregnant during the study and for 6 months after the final study drug administration And have a negative serum pregnancy test at screening And, if heterosexually active, agree to consistently use highly effective contraception per locally accepted standards in addition to a barrier method starting at screening and throughout the study period and for 6 months after final study drug administration.

  8. Females must agree not to breastfeed or donate ova throughout the study drug treatment period and for 6 months after the final study drug administration.
  9. Males (even if surgically sterilized), and their partners who are women of childbearing potential must be using highly effective contraception in addition to a barrier method throughout the study drug treatment period.
  10. Males must not donate sperm throughout the study drug treatment period.
  11. Agrees not to participate in another interventional study while on treatment.
  12. Karnofsky Performance Status 70 or greater is required.

Exclusion Criteria:

  1. Prior participation in an APR-246 study.
  2. Use of umbilical cord blood donor and stem cell source.
  3. Patient has uncontrolled infection.
  4. Use of investigational agent within 14 days of pre-HSCT screening or anytime thereafter.
  5. Use of hypomethylating agent, cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS or AML within 14 days of the first day of pre-HSCT screening or anytime thereafter.
  6. Patient has used experimental therapy for acute GVHD at any time post-transplant.
  7. Patient requires treatment with supplemental oxygen not including usage of non-invasive CPAP (continuous positive airways pressure) at night.
  8. Patient has any of the following cardiac abnormalities (as determined by treating physician):

    1. Myocardial infarct within six months prior to registration
    2. New York Heart Association Class II or worse heart failure or known LVEF (left ventricular ejection fraction) < the institution LLN (lower limit normal)
    3. A history of familial long QT syndrome
    4. Electrocardiographic evidence of acute ischemia at screening
    5. Symptomatic atrial or ventricular arrhythmias not controlled by medications
    6. QTc ≥ 470 ms calculated from a mean of 3 ECG (electrocardiogram) readings using Fridericia's correction (QTcF = QT/RR0.33)
    7. Bradycardia (<40 bpm) at screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03931291


Contacts
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Contact: Eyal Attar, MD +1 617 804 6947 info@aprea.com

Locations
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United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Asmita Mishra, MD, Phd    813-745-8248      
United States, Maryland
Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21278
Contact: Amy Dezern, MD    410-502-7208      
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Yi-Bin Chen, MD    617-726-5765      
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Mahasweta Gooptu, MD    215-450-0161      
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Roni Tamari, MD    212-639-5987      
United States, Tennessee
Vanderbilt Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Micael Byrne, MD    615-835-8135      
United States, Washington
Fred Hutchinson Cancer Center Recruiting
Seattle, Washington, United States, 98109
Contact: Joachim Deeg, MD    206-667-4984      
Sponsors and Collaborators
Aprea Therapeutics AB
Investigators
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Principal Investigator: Asmita Mishra, MD, PhD H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612

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Responsible Party: Aprea Therapeutics AB
ClinicalTrials.gov Identifier: NCT03931291    
Other Study ID Numbers: A19-11172
First Posted: April 30, 2019    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors