Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00013533
Status:
COMPLETED
Last Update Posted:
2019-12-16
First Post:
2001-03-20
Brief Title:
Pilot Study of Non-Myeloablative HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Pilot Study of Non-Myeloablative HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies
Status:
COMPLETED
Status Verified Date:
2015-05-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 CR1 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 CR1 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 20 mgdL and serum ALT and AST values less than or equal to 25x 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 mLmin173 m2
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
InductionConsolidation 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
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 CR1 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 CR1 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 20 mgdL and serum ALT and AST values less than or equal to 25x 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 mLmin173 m2
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
InductionConsolidation 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 CR1 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 CR1 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 20 mgdL and serum ALT and AST values less than or equal to 25x 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 mLmin173 m2
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
InductionConsolidation 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
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 CR1 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 CR1 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 20 mgdL and serum ALT and AST values less than or equal to 25x 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 mLmin173 m2
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
InductionConsolidation 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-C-0125 | None | None | None |