Leukemia Acute Myeloid
Conditions
Keywords
revumenib, azacitidine, venetoclax, allogeneic stem cell transplant
Brief summary
This study is testing a new treatment combination called RAVEN, which includes revumenib, azacitidine, and venetoclax, in patients who are newly diagnosed with a specific type of acute myeloid leukemia (AML) called KMT2A- translocated AML. People with this type of AML often have poor outcomes, so new treatments are needed that may work better and cause fewer side effects. The study has two parts: 1. Induction Phase: Patients will receive treatment for up to 3 cycles. Each cycle lasts 28 days. The goal is to help the leukemia go into remission. 2. Continuation Phase: After remission and blood count recovery, patients will continue treatment until the leukemia returns, side effects become too severe, the patient receives a stem cell transplant, or another reason to stop treatment occurs. Patients who receive an allogeneic stem cell transplant (stem cells from a donor) may also join a separate part of the study to test revumenib as maintenance treatment after transplant.
Interventions
DRUGAzacitidine
Subcutaneous or IV over 10-40 minutes on Days 1-7 or days 1-5, 8-9, in every 28 days, for 3 cycles.
DRUGVenetoclax
Per oral, daily in combination with posaconazole for 1- 28 days, for 3 cycles.
DRUGRevumenib
Per oral,12 hours in combination with posaconazole for 1- 28 days , for 3 cycles.
Sponsors
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study uses a structured, stepwise design. All participants begin with induction therapy. Patients who do not respond discontinue treatment, while those who achieve remission proceed to the continuation phase. During continuation therapy, patients may either remain on treatment until relapse/progression or proceed to allogeneic stem cell transplant.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. * Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee. * Age 18-65 years at the time of consent. * Untreated AML based on 2022 WHO or ICC criteria with KMT2A translocation by local standard diagnostic testing by cytogenetics/karyotype or FISH
Exclusion criteria
* Isolated myeloid sarcoma (patients must have blood or marrow involvement with AML to enter study) * Active central nervous system (CNS) involvement by AML. Of note, patients are eligible if CNS leukemia is in remission at the time of study entry. * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission rate | Up to 3 months | Complete remission (CR) rate will be determined as defined in the protocol Response Criteria. Bone marrow blasts \< 5%; absence of circulating blasts; absence of extramedullary disease; ANC \> 1.0 × 109/L (1,000/μL); platelet count ≥ 100 × 109/L (100 000/μL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite Complete remission | Up to 3 months | Composite Complete remission (CCr) rate defined as complete remission (CR) + complete remission with incomplete recovery (CRi) + complete remission with partial hematologic recovery (CCr)= CR + CRi + CRh. CR: Bone marrow blasts \< 5%; absence of circulating blasts; absence of extramedullary disease; ANC \> 1.0 × 109/L (1,000/μL); platelet count ≥ 100 × 109/L (100 000/μL) CRi = All CR criteria except for residual neutropenia \<1.0 × 109/L (1,000/μL) or thrombocytopenia \< 100× 109/L (100 000/μL CRh: ANC ≥ 0.5 × 109/L (500/μL) and platelet count ≥50 × 109/L (50 000/μL), otherwise all other CR criteria met. |
| Duration of complete remission (DOCR) | Up to 2 years | Duration of complete remission (DOCR) will be defined as the time from the first complete remission to hematological relapse or death from any cause. CR: Bone marrow blasts \< 5%; absence of circulating blasts; absence of extramedullary disease; ANC \> 1.0 × 109/L (1,000/μL); platelet count ≥ 100 × 109/L (100 000/μL) |
| Event-free survival | Up to 2 years | Event-free survival will be determined as time until treatment failure (lack of CRc), relapse or death. |
| The number of treatment-emergent adverse events | Up to 2 years | The number of treatment-emergent special interest (AESIs) and serious adverse events (SAEs), and clinically significant test results will be submitted. |
| Relapse-free survival | Up to 2 years | Relapse-free survival will be determined as time to relapse or death after achieving CR. |
| Overall survival | Up to 2 years | Overall survival will be determined as time until date of death from any cause. |
| MRD-Negative (MRD<0.02%) complete remission | Up to 3 months | MRD-Negative (MRD\<0.02%) complete remission rate will be assessed from bone marrow samples using Hematologics Flow MRD assay after 2 cycles of RAVEN treatment |
Countries
United States
Contacts
CONTACTLauren Higgins
PRINCIPAL_INVESTIGATORJoshua Zeidner, MD
UNC Lineberger Comprehensive Cancer Center
Outcome results
None listed