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

NCT ID: NCT03931291

Last Updated: 2025-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-16
• Study Completion Date: 2022-01-14

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.

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.

Conditions

Acute Myeloid Leukemia or Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental arm: APR-246 + azacitidine

APR-246 and azacitidine maintenance therapy will continue for a maximum of 12 cycles

Group Type: EXPERIMENTAL

APR-246

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Azacitidine

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aprea Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Asmita Mishra, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612

Locations

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Countries

United States

References

Mishra A, Tamari R, DeZern AE, Byrne MT, Gooptu M, Chen YB, Deeg HJ, Sallman D, Gallacher P, Wennborg A, Hickman DK, Attar EC, Fernandez HF. Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for TP53-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2022 Dec 1;40(34):3985-3993. doi: 10.1200/JCO.22.00181. Epub 2022 Jul 11.

Reference Type: DERIVED

PMID: 35816664 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

A19-11172

Identifier Type: -

Identifier Source: org_study_id