Trial Title:
Revumenib for the Treatment of Acute Leukemia in Patients Post-Allogeneic Stem Cell Transplant
NCT ID:
NCT06575296
Condition:
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
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Acute Disease
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (revumenib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration
Arm group label:
Treatment (revumenib)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Treatment (revumenib)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Treatment (revumenib)
Other name:
EC
Intervention type:
Other
Intervention name:
Electronic Health Record Review
Description:
Ancillary studies
Arm group label:
Treatment (revumenib)
Intervention type:
Other
Intervention name:
Quality-of-Life Assessment
Description:
Ancillary studies
Arm group label:
Treatment (revumenib)
Other name:
Quality of Life Assessment
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Treatment (revumenib)
Intervention type:
Drug
Intervention name:
Revumenib
Description:
Given PO
Arm group label:
Treatment (revumenib)
Other name:
Menin-Mixed Lineage Leukemia Protein-Protein Interaction Inhibitor SNDX-5613
Other name:
Menin-MLL Inhibitor SNDX-5613
Other name:
Menin-MLL Interaction Inhibitor SNDX-5613
Other name:
SNDX 5613
Other name:
SNDX-5613
Other name:
SNDX5613
Summary:
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.
Detailed description:
PRIMARY OBJECTIVES:
I. Evaluate the safety and tolerability of revumenib as maintenance therapy in patients
with KMT2A rearranged or NPM1 mutated acute leukemia after undergoing allogeneic
hematopoietic cell transplantation (alloHCT).
II. Determine the recommended phase 2 dose (RP2D) of revumenib as maintenance therapy in
patients with KMT2A rearranged (KMT2Ar) or NPM1 mutated (NPM1m) acute leukemia after
undergoing alloHCT.
SECONDARY OBJECTIVES:
I. Assess overall survival (OS), relapse free survival (RFS), cumulative incidence of
relapse (CIR), and composite graft versus host disease (GVHD)-free, relapse-free survival
(GRFS) at 1 and 2 years from first dose of revumenib.
II. Non-relapse mortality (NRM) at 100 days 1 and 2 years after first dose of revumenib.
III. Evaluate the rate and grading of acute GVHD at 180 days after alloHCT. IV. Evaluate
the incidence and grading of chronic GVHD (cGVHD) at 1 and 2 years after first dose of
revumenib.
V. Evaluate minimal residual disease (MRD) using quantitative polymerase chain reaction
(PCR) (NPM1m) or ClonoSeq (B-acute lymphoblastic leukemia [B-ALL]).
VI. Evaluate MRD using flow cytometry. VII. Evaluate the feasibility of maintenance
therapy.
EXPLORATORY OBJECTIVES:
I. Evaluate immune cell populations and immune reconstitution after maintenance therapy.
II. Evaluate the inflammatory cytokine profile and levels. III. Evaluate detection of
residual NPM1m error-corrected sequencing. IV. Develop and evaluate a novel KMT2Ar assay
in detecting residual disease. V. Evaluate quality of life.
OUTLINE: This is a dose-escalation study of revumenib followed by a dose-expansion study.
Starting 50-150 days after alloHCT, patients receive revumenib orally (PO) once daily
(QD) or every 12 hours on days 1-28 of each cycle. Cycles repeat every 28 days for up to
2 years in the absence of disease progression or unacceptable toxicity. Additionally,
patients undergo bone marrow biopsy during screening and may undergo echocardiography
(ECHO) during screening and as clinically indicated. Patients also undergo bone marrow
aspiration and collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up at 30 days and then every 3
months for up to 2 years post-treatment start.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- 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
- 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
- PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Age: >= 2
years
- 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
- 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
- PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT:
Participant must meet one of the following disease characteristics:
- Confirmed NPM1m AML with at least one of the following additional
characteristics
- FLT3-ITD co-mutation
- Pre-transplant MRD+ disease by flow cytometry or real time polymerase
chain reaction (qPCR)
- Requires more than one AML induction regimen to acquire complete response
(CR)1
- In second or later complete remission
- Confirmed KMT2Ar acute leukemia obtained by fluorescence in situ hybridization
(11q23 MLL-break apart fluorescence in situ hybridization [FISH]) or
next-generation sequencing (NGS)
- 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
- PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT:
Conditioning regimen: investigator's choice based on center guidelines
- PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: GVHD
prophylaxis: investigator's choice based on center guidelines
- PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Patients
receiving menin inhibitors prior to alloHCT are eligible
- 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
- 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
- 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
- Childbearing potential defined as not being surgically sterilized (men and
women) or have not been free from menses for > 1 year (women only)
- 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)
- PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Participant must be eligible for alloHCT by
City of Hope (COH) standard operating procedure (SOP) guidelines
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Patients should be in
complete remission (CR) by day + 30 (± 7 days) post-HCT BM biopsy
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: No evidence of active or
uncontrolled infection at the time of start of revumenib therapy
- 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
- 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)
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Hemoglobin (Hgb) >= 9.
Transfusion or growth factors are not allowed to achieve these levels
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Platelets >= 75 thousand
(k). Transfusion or growth factors are not allowed to achieve these levels
- 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
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: No morphologic evidence
of relapse post-HCT (pre-HCT MRD+ is)
- 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
- 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)
- 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
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Aspartate
aminotransferase (AST) =< 2.5 x ULN
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Alanine aminotransferase
(ALT) =< 2.5 x ULN
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: QTc using Fridericia's
correction (QTcF) =< 450 msec (males) or =< 470 msec (females)
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Ejection fraction (EF) of
>= 50% by echocardiogram or multigated acquisition (MUGA) scan
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Creatinine clearance of
>= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula
Exclusion Criteria:
- PATIENTS WHO ARE SCHEDULED TO UNDERGO HCT OR THOSE WHO HAVE UNDERGONE HCT: Prior
diagnosis of acute promyelocytic leukemia
- 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
- 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)
- 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
- 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)
- 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)
- 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
- PATIENTS WHO HAVE NOT YET UNDERGONE HCT: Hepatitis C, defined as positive HCV
antibody with reflex to positive HCV ribonucleic acid (RNA)
- 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
- 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
- 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)
- 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
- 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)
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Female participant who is
pregnant or lactating
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Participant has a
malabsorption syndrome or other condition that precludes enteral route of
administration
- 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
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Cardiac disease: any of
the following within the 6 months prior to study entry:
- Myocardial infarction
- Uncontrolled/unstable angina
- Congestive heart failure (New York Heart Association Classification class >=
II)
- Life-threatening or uncontrolled arrhythmia
- Cerebrovascular accident
- Transient ischemic attack
- CRITERIA TO PROCEED TO MAINTENANCE THERAPY WITH REVUMENIB: Gastrointestinal disease:
- Any gastrointestinal issue of the upper gastrointestinal (GI) tract likely to
affect oral drug absorption or ingestion (e.g., gastric bypass, gastroparesis,
etc.)
- Cirrhosis with a Child-Pugh score of B or C
- 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
Gender:
All
Minimum age:
2 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Contact:
Last name:
Brian Ball
Phone:
626-218-2405
Email:
brball@coh.org
Contact backup:
Last name:
Brian Ball
Start date:
December 25, 2024
Completion date:
December 20, 2025
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06575296
