Ruxolitinib-Decitabine Intensified Conditioning Regimen for AML: A Randomized Trial

Chinese PLA General Hospital (301 Hospital)

Status and phase: Enrolling; Phase 4

Conditions: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Treatments: Combination Product: Ruxolitinib, Decitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT07101588

S2024-678-01

Details and patient eligibility

About

This study aims to determine whether the recurrence rate of high-risk acute myeloid leukemia CR1 patients who received allogeneic hematopoietic stem cell transplantation with the Ruxolitinib, Decitabine combined with Bu/Cy or BuF intensive pretreatment regimen is reduced compared with the traditional Bu/Cy or BuFpretreatment regimen.

Full description

Allogeneic hematopoietic stem cell transplantation is the only radical treatment for high-risk acute myeloid leukemia (AML), but the traditional Bu/Cy pretreatment regimen is highly toxic and has a high recurrence rate after transplantation (the long-term survival rate is only 10-30%). Although the existing improved regimens such as sequential chemotherapy can reduce the leukemia burden, they lead to prolonged myelosuppression time (17-39 days) and a non-relapse mortality rate as high as 17.2%. There is an urgent need to develop new pretreatment regimens that have both strong anti-leukemia effects and low toxicity.

Studies have found that the JAK-STAT signaling pathway is generally abnormally activated in hematological tumors such as AML. The objective response rate of Ruxolitinib (a JAK1/2 inhibitor) as a monotherapy for relapsed/refractory leukemia reached 45%. When combined with the demethylated drug decitabine, it can synergistically inhibit leukemia cells. Clinical data show that decitabine reduces the recurrence rate after transplantation by 20% (15.0% vs 38.3%), and the combination of the two has good safety. The main adverse reaction is grade 1-2 hematological toxicity.

Our center innovatively proposed the Rux-Dec-mBu/Cy or BuF combined regimen: integrating Ruxolitinib (step-based dose reduction) and decitabine (20mg/m²/d) on the basis of the classic Bu/Cy or BuF. Previous single-arm studies have shown that the one-year recurrence rate of CR1 patients is 0%, and the incidence of toxicity above grade 3 is less than 11%. This study intends to conduct a multicenter randomized controlled trial to verify the superiority of this regimen in reducing recurrence after transplantation in patients with high-risk AML CR1. Its core advantage lies in simultaneously achieving anti-leukemia enhancement (through JAK-STAT targeting and epigenetic regulation) and controllable toxicity (The median grain deficiency time was shortened to 14 days).

Enrollment: 200 estimated patients

Sex: All

Ages: 14 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 1. Acute myeloid leukemia with indications for allogeneic hematopoietic stem cell transplantation, CR1 2) Have HLA-matched sibling donors or haploidentical donors or ≥8/10 HLA-matched unrelated donors 3) The patients' ages range from 12 to 64 years old 4) Liver function: ALT and AST≤2.5 times the upper limit of normal values, bilirubin ≤2 times the upper limit of normal values 5) Renal function: Creatinine ≤ the upper limit of the normal value 6) There are no uncontrollable infections or serious mental and psychological disorders 7) Sign the informed consent form.

Exclusion criteria

• 1. Patients with acute promyelocytic leukemia (M3) 2. One of the donor and recipient is pregnant 3. Suffering from mental illness or other conditions that prevent one from following the plan.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Assigned Interventions

Active Comparator group

Description:

1. Decitabine: 20 mg/m²/day, administered from Day -15 to Day -10. 2. Ruxolitinib(with Voriconazole): * 10 mg twice daily (bid), Day -15 to Day -5 * 5 mg twice daily (bid), Day -4 to Day -3 * 5 mg once daily (Qd), Day -2 3. Busulfan (Bu): 0.8 mg/kg every 6 hours (Q6h), Day -8 to Day -6. 4. Carmustine (BCNU): 250 mg every 8 hours (Q8h), Day -3. 5. Cytarabine (Ara-C): * 4 g/m²/day, Day -10 to Day -9 (for unrelated or haploidentical donors) * 4 g/m²/day, Day -9 only (for matched sibling donors) 6. Cyclophosphamide (CTX): 50 mg/kg/day, Day -5 to Day -4. or Fludarabine 30mg/m2/day, iv, Day -6 to Day -2; 7. Antithymocyte Globulin (ATG): * 10 mg/kg/day, Day -5 to Day -2 (for unrelated or haploidentical donors) * 5 mg/kg/day, Day -5 to Day -2 (for matched sibling donors)

Treatment:

Combination Product: Ruxolitinib, Decitabine

The control group

No Intervention group

Description:

1. Busulfan (Bu): 0.8 mg/kg every 6 hours (Q6h), Day -8 to Day -6. 2. Carmustine (BCNU): 250 mg every 8 hours (Q8h), Day -3. 3. Cytarabine (Ara-C): * 4 g/m²/day, Day -10 to Day -9 (for unrelated or haploidentical donors) * 4 g/m²/day, Day -9 only (for matched sibling donors) 4. Cyclophosphamide (CTX): 50 mg/kg/day, Day -5 to Day -4. or Fludarabine 30mg/m2/day, iv, Day -6 to Day -2; 5. Antithymocyte Globulin (ATG): * 10 mg/kg/day, Day -5 to Day -2 (for unrelated or haploidentical donors) * 5 mg/kg/day, Day -5 to Day -2 (for matched sibling donors)