Venetoclax in Addition to Sequential Conditioning With Fludarabine / Amsacrine / Ara-C (FLAMSA) + Treosulfan for Allogeneic Blood Stem Cell Transplantation in Patients With MDS, CMML or sAML

Sponsor
Heinrich-Heine University, Duesseldorf
Study ID
NCT05807932
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
  • Secondary Acute Myeloid Leukemia

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax — DRUG
    Study treatment consists of the conditioning therapy including 6 or 8 days of Venetoclax treatment.
  • Amsacrine — DRUG
    Amsacrine is part of the conditioning therapy and is administered on day -10 to -7 before allogeneic blood stem cell transplantation
  • Ara-C — DRUG
    Ara-C is part of the conditioning therapy and is administered on day -10 to -7 before allogeneic blood stem cell transplantation
  • Tacrolimus — DRUG
    Tacrolimus is used for prophylaxis of acute and chronic graft-versus-host-disease according to institutional standards.
  • Mycophenolate Mofetil — DRUG
    Mycophenolate Mofetil is used for prophylaxis of acute and chronic graft-versus-host-disease according to institutional standards.

Study Details

This trial aims to find the MTD of Venetoclax when added to Fludarabin, Amsacrine and Ara-C + Treosulfan and to evaluate whether the addition of Venetoclax to sequential conditioning with FLAMSA + Treosulfan is safe for allogeneic blood stem cell transplantation in patients with high-risk MDS, CMML or sAML (FLAMSAClax)

Key Dates

Start date
Jun 26, 2023
Status verified
Apr 2024
Primary completion
Jan 31, 2026
Completion
Jan 30, 2028

Study Design

Enrollment
38 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Venetoclax
    Venetoclax treatment will be started orally once a day with food, one day before FLAMSA conditioning therapy and stopped the day before high-dose Treosulfan. The total duration of treatment with Venetoclax will be 6 days (day -11 to -6 before stem cell infusion). Patients with active disease at transplant will receive a 3-day ramp-up prephase of Ara-C (100mg total dose infused in 1h) with daily increasing doses of Venetoclax to prevent TLS during conditioning. Total treatment duration with Venetoclax in patients with active disease at transplant will be 8 days (day -13 to -6 before stem cell infusion).

Primary Outcome Measure

The primary target variable is safety, defined as the maximal organ toxicity to each organ system according to CTC criteria as well as the number of AEs of grade III or greater within the first 30 days (± 3) after transplantation [ Time Frame: inclusion until day 30 (± 3) after transplantation ]

Central Contacts

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