Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 2:43 AM
Ignite Modification Date:
2025-12-25 @ 2:43 AM
NCT ID:
NCT00013533
Brief Summary:
Background:
* Allogeneic blood and marrow stem cell transplantation (BMT) plays an important role in the curative treatment of a number of pediatric malignancies. Unfortunately, the success of conventional allogeneic BMT is limited in part by the multiple toxicities associated with myeloablative preparative regimens.
* Non-myeloablative pre-transplant regimens are associated with less toxic side effects than standard BMT. Recently, a novel immunosuppressive, non-myeloablative pre-transplant chemotherapy regimen has been shown to facilitate complete donor engraftment in an adult trial at the NCI.
Objectives:
The primary objective of this protocol is to evaluate the efficacy and safety of this treatment approach in pediatric patients with hematopoietic malignancies
Eligibility:
Inclusion Criteria
Age: Patient must be greater than or equal to 5 years and less than 22 years of age.
Diagnosis:
* Hodgkin s and Non-Hodgkin s Lymphoma: Refractory disease or relapse after salvage regimen.
* Acute Myelogenous Leukemia: History of bone marrow relapse in remission (CR) #2 or greater.
* Acute Lymphocytic Leukemia: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).
* Acute Hybrid Leukemia including mixed lineage, biphenotypic and undifferentiated: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).
* Myelodysplastic Syndrome: RAEB or RAEB-t with less than 10% blasts in marrow and blood.
* Chronic Myelogenous Leukemia: Chronic phase or accelerated phase with less than 10% blasts in marrow and blood.
* Juvenile Myelomonocytic Leukemia: less than 10% blasts in marrow and blood.
Prior Therapy: Chemotherapy to achieve above criteria allowed. Prior BMT allowed as long as at least day 100+ post-prior BMT, no evidence of GVHD, and no detectable residual donor chimerism.
Donor: First degree related donors, who are HLA matched (single HLA-A or B locus mismatch allowed), weight greater than or equal to 15 kilograms, and who meet standard donation criteria will be considered. The same donor from a prior BMT is allowed.
ECOG Performance Status: 0, 1, or 2. and life expectancy: greater than 3 months.
Liver Function: Serum direct bilirubin less than 2.0 mg/dL and serum ALT and AST values less than or equal to 2.5x upper limit of normal. (Values above these levels may be accepted if due to malignancy.)
Renal Function: Age adjusted normal serum creatinine or Cr clearance greater than or equal to 60 mL/min/1.73 m(2).
Pulmonary Function: DLCO greater than or equal to 50%.
Cardiac Function: LVEF greater than or equal to 45% by MUGA or LVSF greater than or equal to 28% by ECHO
Exclusion Criteria
* Active CNS malignancy: Tumor mass on CT or leptomeningeal disease. (Patients with a history of CNS involvement and no current evidence of CNS disease are allowed.)
* HIV infection, active hepatitis B or C infection: HbSAg or HCV seropositive and elevated liver transaminases.
* Fanconi Anemia.
* Lactating or pregnant females.
Design:
Pilot Study
* Initial evaluation: Patient and donor will be screened for eligibility. G-CSF primed bone marrow derived stem cells will be collected from the donor.
* Induction/Consolidation chemotherapy: 1 to 3 cycles will be given every 22 days depending on disease response, CD4 count, and toxicities.
* Lymphoma: fludarabine, etoposide, doxorubicin, vincristine, cyclophohamide, prednisone, and filgrastim (EPOCH-fludarabine).
* Leukemia and MDS: Fludarabine, cytarabine, and filgrastim (FLAG).
* Transplantation: Fludarabine and cyclophosphamide will be administered over 4 days followed by bone marrow transplant. Patients will remain hospitalized until bone marrow recovery. Patients will be monitored closely at the NIH for at least 100 days post-BMT.
* Post-transplant CNS prophylaxis for ALL: Standard post-transplant CNS prophylaxis will be employed with intrathecal methotrexate to decrease the risk of CNS relapse for all patients with ALL.
* Total number of recipient and donors to be accrued is 56.
Detailed Description:
Background:
* Allogeneic blood and marrow stem cell transplantation (BMT) plays an important role in the curative treatment of a number of pediatric malignancies. Unfortunately, the success of conventional allogeneic BMT is limited in part by the multiple toxicities associated with myeloablative preparative regimens.
* Non-myeloablative pre-transplant regimens are associated with less toxic side effects than standard BMT. Recently, a novel immunosuppressive, non-myeloablative pre-transplant chemotherapy regimen has been shown to facilitate complete donor engraftment in an adult trial at the NCI.
Objectives:
The primary objective of this protocol is to evaluate the efficacy and safety of this treatment approach in pediatric patients with hematopoietic malignancies
Eligibility:
Inclusion Criteria
Age: Patient must be greater than or equal to 5 years and less than 22 years of age.
Diagnosis:
* Hodgkin s and Non-Hodgkin s Lymphoma: Refractory disease or relapse after salvage regimen.
* Acute Myelogenous Leukemia: History of bone marrow relapse in remission (CR) #2 or greater.
* Acute Lymphocytic Leukemia: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).
* Acute Hybrid Leukemia including mixed lineage, biphenotypic and undifferentiated: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).
* Myelodysplastic Syndrome: RAEB or RAEB-t with less than 10% blasts in marrow and blood.
* Chronic Myelogenous Leukemia: Chronic phase or accelerated phase with less than 10% blasts in marrow and blood.
* Juvenile Myelomonocytic Leukemia: less than 10% blasts in marrow and blood.
Prior Therapy: Chemotherapy to achieve above criteria allowed. Prior BMT allowed as long as at least day 100+ post-prior BMT, no evidence of GVHD, and no detectable residual donor chimerism.
Donor: First degree related donors, who are HLA matched (single HLA-A or B locus mismatch allowed), weight greater than or equal to 15 kilograms, and who meet standard donation criteria will be considered. The same donor from a prior BMT is allowed.
ECOG Performance Status: 0, 1, or 2. and life expectancy: greater than 3 months.
Liver Function: Serum direct bilirubin less than 2.0 mg/dL and serum ALT and AST values less than or equal to 2.5x upper limit of normal. (Values above these levels may be accepted if due to malignancy.)
Renal Function: Age adjusted normal serum creatinine or Cr clearance greater than or equal to 60 mL/min/1.73 m(2).
Pulmonary Function: DLCO greater than or equal to 50%.
Cardiac Function: LVEF greater than or equal to 45% by MUGA or LVSF greater than or equal to 28% by ECHO
Exclusion Criteria
* Active CNS malignancy: Tumor mass on CT or leptomeningeal disease. (Patients with a history of CNS involvement and no current evidence of CNS disease are allowed.)
* HIV infection, active hepatitis B or C infection: HbSAg or HCV seropositive and elevated liver transaminases.
* Fanconi Anemia.
* Lactating or pregnant females.
Design:
Pilot Study
* Initial evaluation: Patient and donor will be screened for eligibility. G-CSF primed bone marrow derived stem cells will be collected from the donor.
* Induction/Consolidation chemotherapy: 1 to 3 cycles will be given every 22 days depending on disease response, CD4 count, and toxicities.
* Lymphoma: fludarabine, etoposide, doxorubicin, vincristine, cyclophohamide, prednisone, and filgrastim (EPOCH-fludarabine).
* Leukemia and MDS: Fludarabine, cytarabine, and filgrastim (FLAG).
* Transplantation: Fludarabine and cyclophosphamide will be administered over 4 days followed by bone marrow transplant. Patients will remain hospitalized until bone marrow recovery. Patients will be monitored closely at the NIH for at least 100 days post-BMT.
* Post-transplant CNS prophylaxis for ALL: Standard post-transplant CNS prophylaxis will be employed with intrathecal methotrexate to decrease the risk of CNS relapse for all patients with ALL.
* Total number of recipient and donors to be accrued is 56.
Study:
NCT00013533
Study Brief:
Protocol Section:
NCT00013533