search
Back to results

Ruxolitinib and Decitabine for High Risk Hematological Malignancies

Primary Purpose

Peripheral Blood Stem Cell Transplantation

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
modified By/Cy conditioning regimen intensified by Ruxolitinib and Decitabine
Sponsored by
Chinese PLA General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Blood Stem Cell Transplantation

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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);

Sites / Locations

  • Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ruxolitinib combined with Decitabine

Arm Description

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),

Outcomes

Primary Outcome Measures

Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria
Defined as the proportion of participants whose underlying malignancy relapsed.

Secondary Outcome Measures

DFS(disease-free survival )
DFS was defined as survival with no evidence of relapse or progression.
TRM(treatment-related mortality )
Defined as the proportion of subjects who died due to causes other than malignancy relapse.
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.
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.
OS(overall survival )
OS was defined as the time from transplantation to death due to any cause.
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.
infection rate
Defined as the proportion of participants who developed all kinds of infection.

Full Information

First Posted
October 3, 2020
Last Updated
October 19, 2020
Sponsor
Chinese PLA General Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT04582604
Brief Title
Ruxolitinib and Decitabine for High Risk Hematological Malignancies
Official Title
Ruxolitinib and Decitabine Intensified Conditioning Regimen for Patients With High Risk Hematological Malignancies Underwenting Allogeneic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
September 1, 2023 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Blood Stem Cell Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ruxolitinib combined with Decitabine
Arm Type
Experimental
Arm Description
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),
Intervention Type
Drug
Intervention Name(s)
modified By/Cy conditioning regimen intensified by Ruxolitinib and Decitabine
Other Intervention Name(s)
Ruxolitinib and Decitabine
Intervention Description
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;
Primary Outcome Measure Information:
Title
Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria
Description
Defined as the proportion of participants whose underlying malignancy relapsed.
Time Frame
365 days after transplantation
Secondary Outcome Measure Information:
Title
DFS(disease-free survival )
Description
DFS was defined as survival with no evidence of relapse or progression.
Time Frame
365 days after transplantation
Title
TRM(treatment-related mortality )
Description
Defined as the proportion of subjects who died due to causes other than malignancy relapse.
Time Frame
365 days after transplantation
Title
Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)
Description
Defined as the proportion of participants who developed acute GVHD.
Time Frame
100 days after transplantation
Title
Number of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria)
Description
Defined as the proportion of participants who developed chronic GVHD.
Time Frame
365 days after transplantation
Title
OS(overall survival )
Description
OS was defined as the time from transplantation to death due to any cause.
Time Frame
365 days after transplantation
Title
GRFS (GVHD free, relapse free survival)
Description
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.
Time Frame
365 days after transplantation
Title
infection rate
Description
Defined as the proportion of participants who developed all kinds of infection.
Time Frame
365 days after transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Relapsed/refractory acute leukemia with indications for allogeneic hematopoietic stem cell transplantation; High risk acute leukemia with indications for allogeneic hematopoietic stem cell transplantation; Medium to high risk myelodysplastic syndrome, myeloproliferative disease, myelodysplastic syndrome/myeloproliferative disease, Chronic myelomonocytic leukemia; Have matched sibling donors, ≥8/10 HLA matched unrelated donors or haploidentical donors All patients should aged 12 to 65 years; Liver function: ALT and AST≤2.5 times the upper limit of normal , bilirubin≤2 times the upper limit of normal; Renal function: creatinine ≤the upper limit of normal; Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness; Eastern Cooperative Oncology Group (ECOG) performance status ≤2; Have signed informed consent. Exclusion Criteria: pregnant women; Patients with mental illness or other states unable to comply with the protocol; AML patients with t (15;17);
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daihong Liu
Phone
86-13681171597
Email
daihongrm@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Liping Dou
Phone
96-13681207138
Email
lipingruirui@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daihong Liu
Organizational Affiliation
Chinese PLA General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100853
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiang Cao
Phone
01066937166

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28619982
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.
Results Reference
background
PubMed Identifier
25516983
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.
Results Reference
background
PubMed Identifier
28484265
Citation
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.
Results Reference
background
PubMed Identifier
31677846
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.
Results Reference
background
PubMed Identifier
29773603
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. No abstract available.
Results Reference
background

Learn more about this trial

Ruxolitinib and Decitabine for High Risk Hematological Malignancies

We'll reach out to this number within 24 hrs