Pilot Study of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies
- Conditions
- Myelodysplastic SyndromeLymphomaLymphocytic LeukemiaAMLHodgkin LymphomaMixed Cell LeukemiaNon Hodgkin's LymphomaCMLALL
- Registration Number
- NCT00013533
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method To determine the efficacy and safety of this chemotherapy regimen in facilitating donor engraftment after allogeneic bone marrow transplantation (BMT). Safety/Efficacy 5 years
- Secondary Outcome Measures
Name Time Method fludarabine-based induction reducing T-cells 5 years immune suppression 5 years IL-7 levels 5 years cytokine profiles 5 years response rates, DFS rates, and incidence and severity ofGVHD following withdrawal of immunosuppression and donorlymphocyte infusions (DLI) for patients who developprogressive disease after day +28 post-transplant 5 years Toxicity of regimen 5 years To determine the toxicity of this non-myelablative allogeneic BMT regimen. incidence and severity of GVHD 5 years response rates and DFS 5 years
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike🇺🇸Bethesda, Maryland, United States