RECRUITING

Revumenib for the Treatment of Acute Leukemia in Patients Post-Allogeneic Stem Cell Transplant

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Conditions

Acute LeukemiaAcute Leukemia of Ambiguous LineageAcute Lymphoblastic LeukemiaAcute Myeloid LeukemiaChildhood Acute LeukemiaChildhood Acute Leukemia of Ambiguous LineageChildhood Acute Lymphoblastic LeukemiaChildhood Acute Myeloid Leukemia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase I trial tests the safety, side effects, best dose and effectiveness of revumenib in treating patients with acute leukemia after allogeneic stem cell transplant. Revumenib is in a class of medications called menin inhibitors. Revumenib targets and binds to the protein menin, thereby preventing the interaction between menin and the mixed lineage leukemia protein. Disrupting this interaction prevents the activation of specific genes that fuel the development of leukemia cells and inhibits the survival, growth, and production of certain kinds of leukemia cells. Giving revumenib may be safe, tolerable, and/or effective in treating patients with acute leukemia after allogeneic stem cell transplant.

Official Title

A Phase I Study of SNDX 5613 (Revumenib) as Post-Transplant Maintenance After Allogeneic Hematopoietic Cell Transplant in Patients With KMT2A-Rearranged or NPM1-Mutated Acute Leukemia

Quick Facts

Study Start:2025-01-25
Study Completion:2028-04-29
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06575296

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:2 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HEMATOPOIETIC CELL TRANSPLANTATION (HCT) OR THOSE WHO HAVE UNDERGONE HCT: Documented informed consent of the participant and/or legally authorized representative
  2. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Agreement to allow the use of archival tissue from diagnostic tumor biopsies; if unavailable, exceptions may be granted with study principal investigator (PI) approval
  3. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participant is willing and able to adhere to the study visit schedule and other protocol requirements
  4. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Age: \>= 2 years
  5. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Have a date for transplant within the next 4 weeks or have received transplant within the last 4 months
  6. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participant was diagnosed with an acute leukemia as defined by the World Health Organization (WHO) 5th edition criteria for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or acute leukemia with ambiguous lineage
  7. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participant must meet one of the following disease characteristics:
  8. * Confirmed NPM1m AML with at least one of the following additional characteristics
  9. * FLT3-ITD co-mutation
  10. * Pre-transplant MRD+ disease by flow cytometry or real time polymerase chain reaction (qPCR)
  11. * Requires more than one AML induction regimen to acquire complete response (CR)1
  12. * In second or later complete remission
  13. * Confirmed KMT2Ar acute leukemia obtained by fluorescence in situ hybridization (11q23 MLL-break apart fluorescence in situ hybridization \[FISH\]) or next-generation sequencing (NGS)
  14. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Any donor (sibling, unrelated, mismatched related/unrelated, cord and haploidentical) or graft source (peripheral blood \[PB\] stem cell or bone marrow \[BM\]) will be included
  15. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Conditioning regimen: investigator's choice based on center guidelines
  16. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: GVHD prophylaxis: investigator's choice based on center guidelines
  17. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Patients receiving menin inhibitors prior to alloHCT are eligible
  18. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Negative serum pregnancy test for female patients of childbearing potential who have already undergone alloHCT
  19. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: If a female of childbearing potential, must be willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose
  20. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: If male of childbearing potential, must agree to use barrier contraception from the time of enrollment through 120 days following the last study drug dose
  21. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  22. * PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Participant has an Eastern Cooperative Oncology Group (ECOG) =\< 2 or Karnofsky Performance Status (KPS) \>= 70, or a Lansky Performance Score of \>= 70 (if aged \< 18 years)
  23. * PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Participant must be eligible for alloHCT by City of Hope (COH) standard operating procedure (SOP) guidelines
  24. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Patients should be in complete remission (CR) by day + 30 (± 7 days) post-HCT BM biopsy
  25. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: No evidence of active or uncontrolled infection at the time of start of revumenib therapy
  26. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has an ECOG =\< 2 or KPS \>= 70, or Lansky Performance Score of \>= 70 if aged \< 18 years
  27. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: No active grade 2-4 acute GVHD (prednisone dose of =\< 0.5 mg/kg daily is allowed)
  28. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Hemoglobin (Hgb) \>= 9. Transfusion or growth factors are not allowed to achieve these levels
  29. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Platelets \>= 75 thousand (k). Transfusion or growth factors are not allowed to achieve these levels
  30. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Patients must be fully engrafted after HCT, defined as absolute neutrophil count (ANC) \>= 500 for 3 days. Patients may NOT be given granulocyte colony-stimulating factor (GCSF) to meet eligibility criteria; however, they may receive GCSF after start of treatment
  31. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: No morphologic evidence of relapse post-HCT (pre-HCT MRD+ is)
  32. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant is between day + 50 and + 150 after first alloHCT with no morphologic evidence of relapse post-HCT
  33. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless considered to be due to Gilbert's syndrome)
  34. * Note: Participants who are \< 75 years of age may have a bilirubin of =\< 3.0 x ULN. Patients with abnormal liver function tests (LFTs) in the context of active GVHD will not be included
  35. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Aspartate aminotransferase (AST) =\< 2.5 x ULN
  36. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Alanine aminotransferase (ALT) =\< 2.5 x ULN
  37. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: QTc using Fridericia's correction (QTcF) =\< 450 msec (males) or =\< 470 msec (females)
  38. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Ejection fraction (EF) of \>= 50% by echocardiogram or multigated acquisition (MUGA) scan
  39. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Creatinine clearance of \>= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula
  1. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Prior diagnosis of acute promyelocytic leukemia
  2. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Participants who are unable to take a strong CYP3A4 inhibitor such as voriconazole or posaconazole. Note: Patients must be taking a strong CYP3A4 inhibiting antifungal at least 7 days prior to starting revumenib cycle 1
  3. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Patients requiring the concurrent use of medications known or suspected to prolong the QT/corrected QT (QTc) interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (e.g., diphenhydramine, famotidine, ondansetron, bactrim, tacrolimus, azoles)
  4. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: History of or any concurrent condition, therapy, laboratory abnormality, or allergy to excipients that in the investigator's opinion might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate
  5. * PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
  6. * PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Participant has detectable human immunodeficiency virus (HIV) viral load within the previous 6 months (must have viral load testing prior to study enrollment if participant has a known history of HIV 1/2 antibodies)
  7. * PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Active uncontrolled hepatitis B or C, defined as hepatitis B or C virus (HBV/HCV) surface antigen positive and HBV/HCV core antibody positive, with positive HBV/HCV deoxyribonucleic acid (DNA), or HBV/HCV positive core antibody alone with positive HBV/HCV DNA
  8. * PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Hepatitis C, defined as positive HCV antibody with reflex to positive HCV ribonucleic acid (RNA)
  9. * PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Other active malignancy; patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  10. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Active grade II-IV acute GVHD, chronic GVHD (moderate or severe) and/or requiring systemic steroids with prednisone dose equivalent of \>= 0.25mg/kg within 4 weeks of revumenib administration
  11. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
  12. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participants who are unable to take a strong CYP3A4 inhibitor such as voriconazole or posaconazole. Note: Patients must be taking a strong CYP3A4 inhibiting antifungal at least 7 days prior to starting revumenib in cycle 1
  13. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Patients requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (e.g., diphenhydramine, famotidine, ondansetron, bactrim, tacrolimus, and azoles)
  14. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Female participant who is pregnant or lactating
  15. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has a malabsorption syndrome or other condition that precludes enteral route of administration
  16. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has chronic respiratory disease that requires continuous oxygen, or significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect participation in this study
  17. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Cardiac disease: any of the following within the 6 months prior to study entry:
  18. * Myocardial infarction
  19. * Uncontrolled/unstable angina
  20. * Congestive heart failure (New York Heart Association Classification class \>= II)
  21. * Life-threatening or uncontrolled arrhythmia
  22. * Cerebrovascular accident
  23. * Transient ischemic attack
  24. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Gastrointestinal disease:
  25. * Any gastrointestinal issue of the upper gastrointestinal (GI) tract likely to affect oral drug absorption or ingestion (e.g., gastric bypass, gastroparesis, etc.)
  26. * Cirrhosis with a Child-Pugh score of B or C
  27. * CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: GVHD: Signs or symptoms of acute or cGVHD \> grade 0 within 4 weeks of enrollment. Patients may be on physiological doses of steroids

Contacts and Locations

Study Contact

Brian Ball, MD
CONTACT
626-218-2405
brball@coh.org

Principal Investigator

Brian Ball, MD
PRINCIPAL_INVESTIGATOR
City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center
Duarte, California, 91010
United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

  • Brian Ball, MD, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-01-25
Study Completion Date2028-04-29

Study Record Updates

Study Start Date2025-01-25
Study Completion Date2028-04-29

Terms related to this study

Additional Relevant MeSH Terms

  • Acute Leukemia
  • Acute Leukemia of Ambiguous Lineage
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Childhood Acute Leukemia
  • Childhood Acute Leukemia of Ambiguous Lineage
  • Childhood Acute Lymphoblastic Leukemia
  • Childhood Acute Myeloid Leukemia