Acute Myeloid Leukemia

Myeloid Neoplasms
Acute Myeloid Leukemia
- Newly Diagnosed
  - Fit for Intensive Therapy
    - FLT3 Positive
    - FLT3-ITD negative
    - Non-genetic Driven
    - Allogenic Transplant
  - VICCCTT26030
    Phase III Mocravimod as Adjunctive and Maintenance Treatment in AML Patients Undergoing Allo-HCT
  - Not Fit for Intensive Therapy
    - FLT3 Positive
      - No Current Trials
    - VICCHEM25012
      Phase 3 Study of Bleximenib, Venetoclax and Azacitidine in AML KMT2A/NPM1 Mutations
    - Non-genetic Driven
- VICC-DTCTT23454
  A Phase III Trial of Tac/MTX/Rux vs PTCy/Tac/MMF in RIC Allogeneic PBSC Transplantation
- VICCCTT25025
  SERENE-T: Phase 2 Trial of AML & MDS Undergoing RIC or NMA Allogeneic HCT with Orca-T
- CIBMTRCTT25029
  Platform Protocol to Investigate PTCy-Based GVHD PPx in Patients w HM Undergoing MMUD PBSCT
- Relapse/Refractory
  - MEIS1 overexpression
  - All Comers
    - VICC-VCHEM23008P
      Phase Ib Study of Eltanexor & Venetoclax in Relapsed or Refractory MDS and Acute AML
  - VICCHEMP25017
    Phase 1 Study of CBX-250 in Participants with R/R AML, HR-MDS or CMML
    - Key inclusion criteria:
      - Participants with histological confirmation of advanced hematologic malignancy including:
      a. R/R AML, as defined by standardized criteria (e.g., European LeukemiaNet criteria [Dohner 2022]; after standard of care therapy. Participants with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment (including HSCT) are eligible.
      b. R/R HR-MDS or very high risk MDS as per the Revised International Prognostic Scoring System (IPSS-R; Greenberg 2012) or Molecular International Prognostic Scoring System (IPPS-M, Bernard 2022) who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
      c. R/R CMML who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine)
      
      - White blood cells must be below 25,000/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
      
      - Historical documented evidence of HLA-A*02:01 allele positivity
      
      -ECOG 0-1
      
      Key exclusion criteria:
      - Previous CTSG targeted therapy or treatment with any pMHC T-cell engager
      
      - Isolated extramedullary relapse.
      
      - Active central nervous system (CNS) disease.
  - VICCHEMP25067
    Phase 1 Study of STX-0712 in Patients with Advanced Hematologic Malignancies
  - VICCCTT26030
    Phase III Mocravimod as Adjunctive and Maintenance Treatment in AML Patients Undergoing Allo-HCT
  - VEN Refractory
    - VICC-VCHEM23008P
      Phase Ib Study of Eltanexor & Venetoclax in Relapsed or Refractory MDS and Acute AML
  - KMT2A / NPM1
    - Fit for Intensive Therapy
      - VICC-DTHEM23484P
        Safety & Tolerb of Ziftomenib Combos for Tx of KMT2A-Rearranged or NPM1-Mutant Relap/Refr AML
        
        o Fit for Intensive Therapy: Tx FLAG-Ida + Ziftomenib
         Inclusion criteria:
        • Age: >18 - <75 years old
        • R/R AML >5% BM blasts or blasts in blood x 2 >1 week apart
        • Confirmed NPM1-mut or KMT2A-r
        • ECOG <2
        • Adequate organ function: AST/ALT <3xULN, T. bili <1.5 ULN, EF >50%, CrCl >50ml/min
         Exclusion criteria:
        • Active CNS disease
        • Uncontrolled infection
        • QTcF >480ms
        • RT/chemo/immune/anti-cancer therapy <14 days or 5 1/2T prior to first dose of study Rx
        • HSCT w/o count recovery
        • Active GvHD
        
        o Unfit for Intensive Therapy: Tx LDAC + Ziftomenib
         Eligibility:
        • Age >18 years old
        • R/R AML >5% BM blasts or blasts in blood x 2 >1 week apart
        • Confirmed NPM1 mutation or KMT2A rearrangement
        • ECOG <2
        • Adequate organ function: AST/ALT <3xULN, T. bili <1.5 ULN, EF >40%, CrCl >50ml/min
         Exclusion criteria:
        • Active CNS disease
        • Uncontrolled infection
        • QTcF >480ms
        • RT/chemo/immune/anti-cancer therapy <14 days or 5 1/2T prior to first dose of study Rx
        • HSCT w/o count recovery
        • Active GvHD
        
        o KMT2A/NPM1 with FLT3 mutation: Tx Gilteritinib + Ziftomenib
         Eligibility:
        • Age >18 years old
        • R/R AML >5% BM blasts or blasts in blood x 2 >1 week apart
        • Confirmed NPM1 mutation or KMT2A rearrangement
        • Confirmed FLT3-ITD/TKD
        • Prior Gilteritinib failure or intolerance
        • ECOG <2
        • Adequate organ function: AST/ALT <3xULN, T. bili <1.5 ULN, EF >40%, CrCl >50ml/min
         Exclusion criteria:
        • Active CNS disease
        • Uncontrolled infection
        • QTcF >480ms
        • RT/chemo/immune/anti-cancer therapy <14 days or 5 1/2T prior to first dose of study Rx
        • HSCT w/o count recovery
        • Active GvHD
    - Not Fit for Intensive Therapy
      - VICC-DTHEM23484P
        Safety & Tolerb of Ziftomenib Combos for Tx of KMT2A-Rearranged or NPM1-Mutant Relap/Refr AML
        
        o Fit for Intensive Therapy: Tx FLAG-Ida + Ziftomenib
         Inclusion criteria:
        • Age: >18 - <75 years old
        • R/R AML >5% BM blasts or blasts in blood x 2 >1 week apart
        • Confirmed NPM1-mut or KMT2A-r
        • ECOG <2
        • Adequate organ function: AST/ALT <3xULN, T. bili <1.5 ULN, EF >50%, CrCl >50ml/min
         Exclusion criteria:
        • Active CNS disease
        • Uncontrolled infection
        • QTcF >480ms
        • RT/chemo/immune/anti-cancer therapy <14 days or 5 1/2T prior to first dose of study Rx
        • HSCT w/o count recovery
        • Active GvHD
        
        o Unfit for Intensive Therapy: Tx LDAC + Ziftomenib
         Eligibility:
        • Age >18 years old
        • R/R AML >5% BM blasts or blasts in blood x 2 >1 week apart
        • Confirmed NPM1 mutation or KMT2A rearrangement
        • ECOG <2
        • Adequate organ function: AST/ALT <3xULN, T. bili <1.5 ULN, EF >40%, CrCl >50ml/min
         Exclusion criteria:
        • Active CNS disease
        • Uncontrolled infection
        • QTcF >480ms
        • RT/chemo/immune/anti-cancer therapy <14 days or 5 1/2T prior to first dose of study Rx
        • HSCT w/o count recovery
        • Active GvHD
        
        o KMT2A/NPM1 with FLT3 mutation: Tx Gilteritinib + Ziftomenib
         Eligibility:
        • Age >18 years old
        • R/R AML >5% BM blasts or blasts in blood x 2 >1 week apart
        • Confirmed NPM1 mutation or KMT2A rearrangement
        • Confirmed FLT3-ITD/TKD
        • Prior Gilteritinib failure or intolerance
        • ECOG <2
        • Adequate organ function: AST/ALT <3xULN, T. bili <1.5 ULN, EF >40%, CrCl >50ml/min
         Exclusion criteria:
        • Active CNS disease
        • Uncontrolled infection
        • QTcF >480ms
        • RT/chemo/immune/anti-cancer therapy <14 days or 5 1/2T prior to first dose of study Rx
        • HSCT w/o count recovery
        • Active GvHD
  - KMT2 / NPM1 with FLT3- ITD mutation
    - VICC-DTHEM23484P
      Safety & Tolerb of Ziftomenib Combos for Tx of KMT2A-Rearranged or NPM1-Mutant Relap/Refr AML
      - o Fit for Intensive Therapy: Tx FLAG-Ida + Ziftomenib
         Inclusion criteria:
        • Age: >18 - <75 years old
        • R/R AML >5% BM blasts or blasts in blood x 2 >1 week apart
        • Confirmed NPM1-mut or KMT2A-r
        • ECOG <2
        • Adequate organ function: AST/ALT <3xULN, T. bili <1.5 ULN, EF >50%, CrCl >50ml/min
         Exclusion criteria:
        • Active CNS disease
        • Uncontrolled infection
        • QTcF >480ms
        • RT/chemo/immune/anti-cancer therapy <14 days or 5 1/2T prior to first dose of study Rx
        • HSCT w/o count recovery
        • Active GvHD
        
        o Unfit for Intensive Therapy: Tx LDAC + Ziftomenib
         Eligibility:
        • Age >18 years old
        • R/R AML >5% BM blasts or blasts in blood x 2 >1 week apart
        • Confirmed NPM1 mutation or KMT2A rearrangement
        • ECOG <2
        • Adequate organ function: AST/ALT <3xULN, T. bili <1.5 ULN, EF >40%, CrCl >50ml/min
         Exclusion criteria:
        • Active CNS disease
        • Uncontrolled infection
        • QTcF >480ms
        • RT/chemo/immune/anti-cancer therapy <14 days or 5 1/2T prior to first dose of study Rx
        • HSCT w/o count recovery
        • Active GvHD
        
        o KMT2A/NPM1 with FLT3 mutation: Tx Gilteritinib + Ziftomenib
         Eligibility:
        • Age >18 years old
        • R/R AML >5% BM blasts or blasts in blood x 2 >1 week apart
        • Confirmed NPM1 mutation or KMT2A rearrangement
        • Confirmed FLT3-ITD/TKD
        • Prior Gilteritinib failure or intolerance
        • ECOG <2
        • Adequate organ function: AST/ALT <3xULN, T. bili <1.5 ULN, EF >40%, CrCl >50ml/min
         Exclusion criteria:
        • Active CNS disease
        • Uncontrolled infection
        • QTcF >480ms
        • RT/chemo/immune/anti-cancer therapy <14 days or 5 1/2T prior to first dose of study Rx
        • HSCT w/o count recovery
        • Active GvHD
- Post-Allogenic Transplant
  - Fit for Intensive Therapy
  - VICC-VCHEM23008P
    Phase Ib Study of Eltanexor & Venetoclax in Relapsed or Refractory MDS and Acute AML
- Acute Promyelocytic Leukemia
  - No Current Trials