Ruxolitinib and Decitabine for High Risk Hematological Malignancies

Peripheral Blood Stem Cell Transplantation Clinical Trial

Official title:

Ruxolitinib and Decitabine Intensified Conditioning Regimen for Patients With High Risk Hematological Malignancies Underwenting Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04582604
• Other study ID #: S2020-297-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 1, 2020
• Est. completion date: September 30, 2025

Study information

• Verified date: October 2020
• Source: Chinese PLA General Hospital
• Contact: Daihong Liu
• Phone: 86-13681171597
• Email: daihongrm[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 30, 2025
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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);

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Peripheral Blood Stem Cell Transplantation

Intervention

Drug:
• modified By/Cy conditioning regimen intensified by Ruxolitinib and Decitabine
Day -15 to -14 : Decitabine 20 mg/m2/day, Ruxolitinib 70mg bid; Day-10: Cytarabine 1.6 g/m2/day CI (only for Haploidentical and unrelated donor), Ruxolitinib 60mg bid; Day- 9: Cytarabine 4g/m2/day CI, Ruxolitinib 60mg bid; Day- 8 to -7: Busulfan 0.8mg/kg Q6h iv, Ruxolitinib 50mg bid; Day-6: Busulfan 0.8mg/kg Q6h iv, Ruxolitinib 40mg bid; Day-5: Cyclophosphamide 1.8 g/m2/day CI, Ruxolitinib 30mg bid; Day-4: Cyclophosphamide 1.8 g/m2/day CI, Ruxolitinib 20mg bid; Day-3: Carmustine 250mg/m2/day iv, Ruxolitinib 10mg bid; Day-2: Ruxolitinib 5mg bid; Day-1: Ruxolitinib 5mg qd;

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

Delgado-Martin C, Meyer LK, Huang BJ, Shimano KA, Zinter MS, Nguyen JV, Smith GA, Taunton J, Winter SS, Roderick JR, Kelliher MA, Horton TM, Wood BL, Teachey DT, Hermiston ML. JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. Leukemia. 2017 Dec;31(12):2568-2576. doi: 10.1038/leu.2017.136. Epub 2017 May 9. — View Citation

Ding YY, Stern JW, Jubelirer TF, Wertheim GB, Lin F, Chang F, Gu Z, Mullighan CG, Li Y, Harvey RC, Chen IM, Willman CL, Hunger SP, Li MM, Tasian SK. Clinical efficacy of ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with GOLGA5-JAK2 fusion and induction failure. Haematologica. 2018 Sep;103(9):e427-e431. doi: 10.3324/haematol.2018.192088. Epub 2018 May 17. — View Citation

Karjalainen R, Pemovska T, Popa M, Liu M, Javarappa KK, Majumder MM, Yadav B, Tamborero D, Tang J, Bychkov D, Kontro M, Parsons A, Suvela M, Mayoral Safont M, Porkka K, Aittokallio T, Kallioniemi O, McCormack E, Gjertsen BT, Wennerberg K, Knowles J, Heckman CA. JAK1/2 and BCL2 inhibitors synergize to counteract bone marrow stromal cell-induced protection of AML. Blood. 2017 Aug 10;130(6):789-802. doi: 10.1182/blood-2016-02-699363. Epub 2017 Jun 15. — View Citation

Rampal R, Ahn J, Abdel-Wahab O, Nahas M, Wang K, Lipson D, Otto GA, Yelensky R, Hricik T, McKenney AS, Chiosis G, Chung YR, Pandey S, van den Brink MR, Armstrong SA, Dogan A, Intlekofer A, Manshouri T, Park CY, Verstovsek S, Rapaport F, Stephens PJ, Miller VA, Levine RL. Genomic and functional analysis of leukemic transformation of myeloproliferative neoplasms. Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):E5401-10. doi: 10.1073/pnas.1407792111. Epub 2014 Dec 2. — View Citation

Venugopal S, Bar-Natan M, Mascarenhas JO. JAKs to STATs: A tantalizing therapeutic target in acute myeloid leukemia. Blood Rev. 2020 Mar;40:100634. doi: 10.1016/j.blre.2019.100634. Epub 2019 Oct 25. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria	Defined as the proportion of participants whose underlying malignancy relapsed.	365 days after transplantation
Secondary	DFS(disease-free survival )	DFS was defined as survival with no evidence of relapse or progression.	365 days after transplantation
Secondary	TRM(treatment-related mortality )	Defined as the proportion of subjects who died due to causes other than malignancy relapse.	365 days after transplantation
Secondary	Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)	Defined as the proportion of participants who developed acute GVHD.	100 days after transplantation
Secondary	Number of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria)	Defined as the proportion of participants who developed chronic GVHD.	365 days after transplantation
Secondary	OS(overall survival )	OS was defined as the time from transplantation to death due to any cause.	365 days after transplantation
Secondary	GRFS (GVHD free, relapse free survival)	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.	365 days after transplantation
Secondary	infection rate	Defined as the proportion of participants who developed all kinds of infection.	365 days after transplantation