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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 high-risk acute leukemia.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| total body irradiation | Active Comparator | 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. |
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| total marrow and lymphoid irradiation | Experimental | Patient receives preparative therapy including cyclophosphamide and total marrow and lymphoid irradiation of 12-20 Gy on Days -8 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| total body irradiation | Radiation | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 100 days after stem cell infusion |
| Progression-Free Survival (PFS) | Calculated using the Kaplan-Meier method. The cumulative incidence of relapse/progression will be calculated as a competing risk using the Gray method. | The time from start of protocol therapy to death, relapse/progression, or last follow-up, whichever comes first, assessed up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of transplantation-related mortality | In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation. | 6 months |
| Incidence of grade II-IV acute graft-versus-host disease (GVHD) after transplantation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xiao Lou, M.D., Ph.D. | Contact | +8610-66947122 | louxiao@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Hu Chen, M.D., Ph.D. | Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA) | Recruiting | Beijing | Beijing Municipality | 100071 | China |
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| ID | Term |
|---|---|
| D014916 | Whole-Body Irradiation |
| D015182 | Lymphatic Irradiation |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
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| total marrow and lymphoid irradiation | Radiation | 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 12-20 Gy TMLI (fraction size of 4 Gy given once a day). Procedure: Peripheral blood stem cell transplantation product will be infused via intravenous drip on Day 0. |
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Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host. |
| Day +100 |
| 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. | 1 Year |
| Incidence of relapse after transplantation | The return of disease after its apparent recovery/cessation. | 1 year and 2 years |
| Menstrual recovery after transplantation | The percentage of female patients who have resumed menses is usually considered as related to ovarian function. | 1 year and 2 years |
| Overall survival after transplantation | 1 year and 2 years | 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. |