Venetoclax in Combination With Non-myeloablative Conditioning Allogeneic Haematopoietic Stem Cell Transplantation

Sponsor
Melbourne Health
Study ID
NCT05005299
Phase
PHASE1
Status
Unknown

Conditions

  • Leukemia, Lymphoblastic, Acute, L1
  • Leukemia, Lymphoblastic, Acute, L2
  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndromes
  • Non-hodgkin Lymphoma
  • Plasma Cell Myeloma

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax — DRUG
    Venetoclax is administered as an oral tablet once daily.
  • Fludarabine — DRUG
    Fludarabine is administered as an intravenous infusion at a dose of 30mg/m2 daily, to be administered over 30 minutes.
  • Cyclophosphamide — DRUG
    Cyclophosphamide is administered as an intravenous infusion at a dose of 750mg/m2 daily, to be administered over 30 minutes and to commence 1 hour after fludarabine infusion.

Study Details

This is a Phase 1, open-label, single center study of short-course oral venetoclax therapy prior to non-myeloablative conditioning with fludarabine and cyclophosphamide in subjects with haematological malignancies who are planned for allogeneic stem cell transplantation (alloSCT). The primary study objective is to determine the safety and maximum tolerated dose of venetoclax when used in combination with fludarabine and cyclophosphamide conditioning. Secondary objectives were to evaluate the transplant outcomes and donor/recipient engraftment of this regimen.

Key Dates

Start date
Jun 8, 2022
Status verified
Jun 2023
Primary completion
Mar 31, 2026
Completion
Mar 31, 2026

Study Design

Enrollment
18 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose Level A
    Subjects will receive receive short-course venetoclax on day -11 to -6 \[venetoclax 100mg daily administered on day -11 to -6 (total venetoclax dose: 600mg)\], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.
  • Experimental: Dose Level B
    Subjects will receive receive short-course venetoclax on day -11 to -6 \[venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10 to -6 (total venetoclax dose: 1100mg)\], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.
  • Experimental: Dose Level C
    Subjects will receive receive short-course venetoclax on day -11 to -6 \[venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10, 400mg daily administered on day -9 and 600mg daily administered on day -8 to -6 (total venetoclax dose: 2500mg)\], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.
  • Experimental: Dose Level B'
    Subjects will receive receive short-course venetoclax on day -11 to -6 \[venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10 and 400mg daily administered on day -9 to -6 (total venetoclax dose: 1900mg)\], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.

Primary Outcome Measure

The development of any dose-limiting toxicities [ Time Frame: Time point between time of first dose of venetoclax to day 30 post-alloSCT ]

Central Contacts

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