Ruxolitinib and Decitabine for High Risk Hematological Malignancies

Phase 1

Recruiting

• Conditions: Peripheral Blood Stem Cell Transplantation
• Interventions: Drug: modified By/Cy conditioning regimen intensified by Ruxolitinib and Decitabine

• Registration Number: NCT04582604
• Lead Sponsor: Chinese PLA General Hospital

Brief Summary

The purpose of this study is to determine the efficacy and safety of Ruxolitinib and Decitabine intensified Conditioning Regimen in Patients with High Risk hematological malignancies undergoing allogeneic peripheral blood stem cell transplantation.

Detailed Description

Allogeneic hematopoietic stem cell transplantation should be offered to eligible patients with high risk hematological malignancies whenever feasible. To further improve the outcome of transplantation patients with high risk hematological malignancies, the investigators developed a modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Decitabine. In this study, the investigators tested the efficacy and feasibility of the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Decitabine in Patients with high risk hematological malignancies undergoing allogeneic peripheral blood stem cell transplantation.

Study Timeline

• Study Start: 2020-09-01
• Status Verified: 2020-10
• Study First Submitted: 2020-10-03
• Study First Submitted QC: 2020-10-03
• Study First Posted: 2020-10-09
• Last Update Submitted: 2020-10-19
• Last Update Posted: 2020-10-20
• Primary Completion: 2023-09-01
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Relapsed/refractory acute leukemia with indications for allogeneic hematopoietic stem cell transplantation; High risk acute leukemia with indications for allogeneic hematopoietic stem cell transplantation;
2. Medium to high risk myelodysplastic syndrome, myeloproliferative disease, myelodysplastic syndrome/myeloproliferative disease, Chronic myelomonocytic leukemia;
3. Have matched sibling donors, ≥8/10 HLA matched unrelated donors or haploidentical donors
4. All patients should aged 12 to 65 years;
5. Liver function: ALT and AST≤2.5 times the upper limit of normal , bilirubin≤2 times the upper limit of normal;
6. Renal function: creatinine ≤the upper limit of normal;
7. Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness;
8. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
9. Have signed informed consent.

Exclusion Criteria

1. pregnant women;
2. Patients with mental illness or other states unable to comply with the protocol;
3. AML patients with t (15;17);

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ruxolitinib combined with Decitabine	modified By/Cy conditioning regimen intensified by Ruxolitinib and Decitabine	Ruxolitinib and Decitabine conditioning regimen All recipients in this arm received the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Decitabine. The conditioning regimen for allogeneic hematopoietic stem cell transplantation consist of ruxolitinib (35 mg bid \[p.o.\], days -15 to -10, diminishing to day -1), decitabine (20 mg/m2/day, days -15 to -10), cytarabine (4 g/m2/day, days -10 to -9 (for unrelated donors or haploidentical donors; and 4 g/m2/day, days -9 for sibling donors)), busulfan (0.8mg/kg, Q6h, days -8 to -6), cyclophosphamide (1.8 g/m2/day, days -5 to -4);carmustine(BCNU)(250mg/m2/day, day -3),

Primary Outcome Measures

Name	Time	Method
Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria	365 days after transplantation	Defined as the proportion of participants whose underlying malignancy relapsed.

Secondary Outcome Measures

Name	Time	Method
Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)	100 days after transplantation	Defined as the proportion of participants who developed acute GVHD.
DFS(disease-free survival )	365 days after transplantation	DFS was defined as survival with no evidence of relapse or progression.
TRM(treatment-related mortality )	365 days after transplantation	Defined as the proportion of subjects who died due to causes other than malignancy relapse.
OS(overall survival )	365 days after transplantation	OS was defined as the time from transplantation to death due to any cause.
GRFS (GVHD free, relapse free survival)	365 days after transplantation	GVHD-free, relapse-free survival (GRFS) was defined as survival with no evidence of grade III-IV acute GVHD or cGVHD requiring immunosuppressive treatment, and without disease recurrence or death from any cause during the first year after transplantation.
Number of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria)	365 days after transplantation	Defined as the proportion of participants who developed chronic GVHD.
infection rate	365 days after transplantation	Defined as the proportion of participants who developed all kinds of infection.

Trial Locations

Locations (1)

Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China