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

NCT ID: NCT07101588

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-01
• Study Completion Date: 2028-12-30

Brief Summary

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.

Detailed 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).

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Assigned Interventions

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)

Group Type: ACTIVE_COMPARATOR

Ruxolitinib, Decitabine

Intervention Type: COMBINATION_PRODUCT

1. Decitabine: 20 mg/m²/day, administered from Day -15 to Day -10.

2. Ruxolitinib:

• 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

The control group

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)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Ruxolitinib, Decitabine

1. Decitabine: 20 mg/m²/day, administered from Day -15 to Day -10.

2. Ruxolitinib:

• 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

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Zhengzhou University, Zhengzhou

UNKNOWN

Sponsor Role: collaborator

Peking University People's Hospital

OTHER

Sponsor Role: collaborator

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Daihong Liu

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Li-ping Dou, Dr.

Role: CONTACT

lipingruirui@163.com

86-10-66937079

Dai-hong Liu, Dr.

Role: CONTACT

lipingruirui@163.com

86-10-66937079

Facility Contacts

Dai-hong Liu, Dr.

Role: primary

daihongrm@163.com

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Other Identifiers

S2024-678-01

Identifier Type: -

Identifier Source: org_study_id