Last updated on April 2010

Chemotherapy Followed by Allogeneic Stem Cell Transplantation in Treating Children With Hematologic Cancer


Brief description of study

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine after the transplant may stop this from happening. PURPOSE: This phase I/II trial is studying how well combination chemothearpy, low-dose chemotherapy, and allogeneic stem cell transplant work in treating children with hematologic cancers.

Detailed Study Description

OBJECTIVES: Primary - Determine the efficacy and safety of non-myeloablative chemotherapy in facilitating donor engraftment after allogeneic stem cell transplantation with G-CSF mobilized peripheral blood stem cells in patients with pediatric hematopoietic malignancies. (Cohort 1) (closed to accrual as of 09/29/2005) - Determine the efficacy and safety of non-myeloablative chemotherapy in facilitating donor engraftment after allogeneic stem cell transplantation with G-CSF primed bone marrow derived stem cells in these patients. (Cohort 2) Secondary - Determine the toxicity of this regimen in these patients. (Cohorts 1 and 2) - Evaluate the ability of this non-myeloablative chemotherapy regimen to reduce the peripheral blood T-cell count in these patients. (Cohorts 1 and 2) - Correlate IL-7 levels with immune suppression and recovery in patients treated with these regimens. (Cohorts 1 and 2) - Correlate cytokine profiles with treatment and graft-versus-host disease (GVHD) in patients treated with this regimen. (Cohort 1) (closed to accrual as of 09/29/2005) - Determine response rates and disease-free survival rates in patients treated with these regimens. (Cohorts 1 and 2) - Determine the incidence and severity of GVHD in patients achieving donor engraftment after treatment with these regimens. (Cohorts 1 and 2) - Determine response rates, disease-free survival rates, and incidence and severity of GVHD after withdrawal of immunosuppression and donor lymphocyte infusions for patients who develop progressive disease after day 28 post-transplantation. (Cohorts 1 and 2) OUTLINE: - Harvest: Donors undergo mobilization of peripheral blood stem cells (cohort 1) (closed to accrual as of 09/29/05) or bone marrow derived stem cells by bone marrow harvest (cohort 2). - Induction: Patients with lymphoma receive fludarabine IV over 30 minutes on days 1-3 and etoposide, doxorubicin, and vincristine IV over 24 hours daily on days 1-4. Patients also receive cyclophosphamide IV over 30 minutes on day 5, oral prednisone 2-4 times daily on days 1-5, and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover. Patients with leukemia or myelodysplastic syndromes receive fludarabine IV over 30 minutes and cytarabine IV over 4 hours on days 1-5. Patients also receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover. For all patients, treatment repeats every 21 days for up to 3 courses until the target absolute CD4 count is achieved. - Preparative regimen: On day 22 after the final course of induction chemotherapy, patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours once daily for 4 days (transplantation days -6 to -3). - Transplantation: Patients are assigned to 1 of 2 cohorts based on time of study entry. - Cohort 1 (closed to accrual as of 09/29/2005): Patients receive G-CSF mobilized peripheral blood stem cells on day 0 and G-CSF once daily beginning on day 0 and continuing until blood counts recover. - Cohort 2: Patients receive allogeneic G-CSF-primed bone marrow derived stem cells on day 0 and G-CSF SC once daily beginning on day 0 and continuing until blood counts recover. - Post-transplant CNS prophylaxis (for patients with acute lymphocytic leukemia): Patients receive standard post-transplant CNS prophylaxis comprising intrathecal methotrexate. - Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily beginning on day -1 and, once oral medications are tolerated, continuing orally twice daily until day 100 followed by a taper until day 180. Patients with progressive disease on day 28 post-transplantation may undergo donor lymphocyte infusions (DLI). Immunosuppression is withdrawn and patients receive nonmobilized DLI IV every 2-4 weeks in the presence of progressive disease and the absence of GVHD. After completion of study treatment, patients are followed periodically for at least 5 years. PROJECTED ACCRUAL: A total of 56 patients (10 recipient/donor pairs in cohort 1 and 18 recipient/donor pairs in cohort 2) will be accrued for this study .

Clinical Study Identifier: NCT00020592

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Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, MD United States
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