Back to resultsTotal Marrow and Lymphoid Irradiation and Chemotherapy for Myelodysplastic Syndrome or Acute Leukemia
Primary Purpose
Myelodysplastic Syndromes, Acute Leukemia
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
total body irradiation
total marrow and lymphoid irradiation
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndromes
Eligibility Criteria
Inclusion Criteria:
- Myelodysplastic syndrome with excess blasts: Cytopenias, Unilineage or multilineage dysplasia, 5-19% blasts in bone marrow.
- Acute lymphocytic leukemia or acute myelogenous leukemia who are in first remission or second remission.
- Karnofsky performance status (KPS) >= 70%
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical siblings who is willing to donate primed blood stem cells or a 10/10 allele matched unrelated donor; a single allele mismatch at A, B, C, DR or DQ and a killer immunoglobulin-like receptor (KIR) mismatch at C will be allowed; all ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques (red cell exchange or plasma exchange)
- A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of >= 50% established by multi gated acquisition scan (MUGA) or echocardiogram
- Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance > 80 ml/min
- Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal (ULN)
- Pulmonary function: Carbon Monoxide Diffusing Capacity corrected (DLCOcorr) > 50% of normal, (oxygen saturation [>92%] can be used in child where pulmonary function tests (PFT's) cannot be obtained)
- The time from the end last induction or re-induction attempt should be greater than or equal to 14 days
- All subjects must have the ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
- Diagnosed extramedullary leukemia
- Active uncontrolled infection at time of enrollment or documented fungal infection within 3 months.
- Evidence of Human immunodeficiency virus (HIV) infection
- Prior myeloablative transplant within the last 6 months
- Prior radiation therapy that would exclude the use of TMLI
- Relapsed patients who have undergone autologous or allogeneic hematopoietic stem cell transplantation previously
Sites / Locations
- Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
total body irradiation
total marrow and lymphoid irradiation
Arm Description
Patient receives preparative therapy including cyclophosphamide and total body irradiation (TBI) of 10 Gy on Days -4 through -1, and starts immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes, followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating factor administration.
Patient receives preparative therapy including cyclophosphamide and total marrow and lymphoid irradiation of 12 Gy on Days -6 through -2, and starts immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes, followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating factor administration.
Outcomes
Primary Outcome Measures
Incidence of toxicity, scored on National Cancer Institute Common Terminology Criteria version 4.03
Toxicity information recorded will include the type, severity, and the probable association with the study regimen.
Hematopoietic reconstruction
Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 1,000 cells/mm3 (1.0×109/L) or greater.
Platelet engraftment is defined as 20,000/mm3 (20×109/L) for 3 consecutive days unsupported by a platelet transfusion.
Secondary Outcome Measures
Incidence of grade II-IV acute graft-versus-host disease (GVHD) after transplantation
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Incidence of chronic GVHD after transplantation
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Menstrual recovery after transplantation
The percentage of female patients who have resumed menses is usually considered as related to ovarian function.
Overall survival after transplantation
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer.
Full Information
NCT ID
NCT03408210
First Posted
December 24, 2017
Last Updated
January 16, 2018
Sponsor
Affiliated Hospital to Academy of Military Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT03408210
Brief Title
Total Marrow and Lymphoid Irradiation and Chemotherapy for Myelodysplastic Syndrome or Acute Leukemia
Official Title
Total Marrow and Lymphoid Irradiation and Chemotherapy Prior to Allogeneic Hematopoietic Cell Transplant for Myelodysplastic Syndrome or Acute Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Unknown status
Study Start Date
March 2014 (Actual)
Primary Completion Date
March 2018 (Anticipated)
Study Completion Date
August 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Affiliated Hospital to Academy of Military Medical Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
RATIONALE: Giving chemotherapy and total marrow and lymphoid irradiation before allogeneic hematopoietic cell transplant helps stop the growth of leukemia cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may achieve brand new hematopoietic recovery. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells, resulting in graft versus-host disease.
PURPOSE: This study is to evaluate the toxicity and efficacy of total marrow and lymphoid irradiation conditioning when given together with combination chemotherapy and allogeneic peripheral blood stem cell transplant in treating patients with myelodysplastic syndrome or acute leukemia.
Detailed Description
Patient receives preparative therapy including cyclophosphamide and total body irradiation (TBI) of 10 Gy or total marrow and lymphoid irradiation (TMLI) of 12-20 Gy, and starts immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes, followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating factor administration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes, Acute Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
191 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
total body irradiation
Arm Type
Active Comparator
Arm Description
Patient receives preparative therapy including cyclophosphamide and total body irradiation (TBI) of 10 Gy on Days -4 through -1, and starts immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes, followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating factor administration.
Arm Title
total marrow and lymphoid irradiation
Arm Type
Experimental
Arm Description
Patient receives preparative therapy including cyclophosphamide and total marrow and lymphoid irradiation of 12 Gy on Days -6 through -2, and starts immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes, followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating factor administration.
Intervention Type
Radiation
Intervention Name(s)
total body irradiation
Other Intervention Name(s)
TBI
Intervention Description
Drug: Cyclophosphamide 60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg
Drug: Cyclosporine or tacrolimus Beginning on Day -1 pre-transplant maintaining a level of 150-250 ng/ml or 5-10 ng/ml respectively. Cyclosporine or tacrolimus dosing will be monitored and altered as clinically appropriate by physician, and discontinue at approximately day + 180 post-transplant.
Drug: Methotrexate 15 mg/m2 intravenous on days 1, 10 mg/m2 intravenous on days 3, 6 and 11 after transplantation.
Intervention: Total Body Irradiation Dose of 10 Gy TBI (fraction size of 5 Gy given once a day on days -2 and -1).
Procedure: Peripheral blood stem cell transplantation product will be infused via intravenous drip on Day 0.
Intervention Type
Radiation
Intervention Name(s)
total marrow and lymphoid irradiation
Other Intervention Name(s)
TMLI
Intervention Description
Drug: Cyclophosphamide 60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg
Drug: Cyclosporine or tacrolimus Beginning on Day -1 pre-transplant maintaining a level of 150-250 ng/ml or 5-10 ng/ml respectively. Cyclosporine or tacrolimus dosing will be monitored and altered as clinically appropriate by physician, and discontinue at approximately day + 180 post-transplant.
Drug: Methotrexate 15 mg/m2 intravenous on days 1, 10 mg/m2 intravenous on days 3, 6 and 11 after transplantation.
Intervention: Total Marrow and Lymphoid Irradiation Dose of 12 Gy TMLI (fraction size of 4 Gy given once a day on days -6, -5 and -4).
Procedure: Peripheral blood stem cell transplantation product will be infused via intravenous drip on Day 0.
Primary Outcome Measure Information:
Title
Incidence of toxicity, scored on National Cancer Institute Common Terminology Criteria version 4.03
Description
Toxicity information recorded will include the type, severity, and the probable association with the study regimen.
Time Frame
Up to 100 days after stem cell infusion
Title
Hematopoietic reconstruction
Description
Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 1,000 cells/mm3 (1.0×109/L) or greater.
Platelet engraftment is defined as 20,000/mm3 (20×109/L) for 3 consecutive days unsupported by a platelet transfusion.
Time Frame
Day +30
Secondary Outcome Measure Information:
Title
Incidence of grade II-IV acute graft-versus-host disease (GVHD) after transplantation
Description
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame
Day +100
Title
Incidence of chronic GVHD after transplantation
Description
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Time Frame
1 Year
Title
Menstrual recovery after transplantation
Description
The percentage of female patients who have resumed menses is usually considered as related to ovarian function.
Time Frame
1 Year and 2 years
Title
Overall survival after transplantation
Description
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer.
Time Frame
1 year and 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Myelodysplastic syndrome with excess blasts: Cytopenias, Unilineage or multilineage dysplasia, 5-19% blasts in bone marrow.
Acute lymphocytic leukemia or acute myelogenous leukemia who are in first remission or second remission.
Karnofsky performance status (KPS) >= 70%
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical siblings who is willing to donate primed blood stem cells or a 10/10 allele matched unrelated donor; a single allele mismatch at A, B, C, DR or DQ and a killer immunoglobulin-like receptor (KIR) mismatch at C will be allowed; all ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques (red cell exchange or plasma exchange)
A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of >= 50% established by multi gated acquisition scan (MUGA) or echocardiogram
Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance > 80 ml/min
Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal (ULN)
Pulmonary function: Carbon Monoxide Diffusing Capacity corrected (DLCOcorr) > 50% of normal, (oxygen saturation [>92%] can be used in child where pulmonary function tests (PFT's) cannot be obtained)
The time from the end last induction or re-induction attempt should be greater than or equal to 14 days
All subjects must have the ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
Diagnosed extramedullary leukemia
Active uncontrolled infection at time of enrollment or documented fungal infection within 3 months.
Evidence of Human immunodeficiency virus (HIV) infection
Prior myeloablative transplant within the last 6 months
Prior radiation therapy that would exclude the use of TMLI
Relapsed patients who have undergone autologous or allogeneic hematopoietic stem cell transplantation previously
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiao Lou, M.D., Ph.D.
Phone
+8610-66947122
Email
louxiao@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hu Chen, M.D., Ph.D.
Organizational Affiliation
Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100071
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiao Lou, M.D., Ph.D.
Phone
+8610-66947122
Email
louxiao@163.com
12. IPD Sharing Statement
Learn more about this trial
Total Marrow and Lymphoid Irradiation and Chemotherapy for Myelodysplastic Syndrome or Acute Leukemia
We'll reach out to this number within 24 hrs