Lymphoma Clinical Trial
Official title:
Pilot Study of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies
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.
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.
;
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