Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

Study Overview
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Brief Summary
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RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer or abnormal 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 cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil before the transplant may stop this from happening. PURPOSE: This clinical trial is studying how well umbilical cord blood stem cell transplant works in treating patients with hematologic cancer or other disease.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of double umbilical cord blood stem cell transplantation using a conditioning regimen comprising lower doses of busulfan and fludarabine phosphate and low-dose total body irradiation, in terms of stem cell engraftment at 60 days post transplantation, in patients with hematologic cancer or other diseases. Determine the merits of conducting a larger, comparative study of this regimen. Secondary Determine mortality within 100 days of transplantation in these patients. OUTLINE: This is a pilot study. Reduced-intensity conditioning regimen: Patients receive busulfan IV over 3 hours on days -9 to -8 and fludarabine phosphate IV on days -7 to -3. Patients then undergo low-dose total body irradiation on day 0. Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV twice daily and mycophenolate orally or IV three times daily beginning on day -3. CNS prophylaxis and/or treatment: Patients with a history of CNS involvement receive prophylactic cytarabine (Ara-C) intrathecally (IT) prior to transplant. Patients also undergo lumbar puncture (LP) to test for active CNS disease. Patients with cerebrospinal fluid positive for leukemia receive Ara-C IT every 2-3 days until a repeat LP shows no remaining leukemic cells. Three days after the last LP and after one final dose of Ara-C, patients begin the conditioning regimen. Double umbilical cord blood (UCB) donor stem cell transplantation (SCT): Patients undergo double UCB donor SCT on day 0. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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A Pilot Study of Double Cord Blood Stem Cell Transplantation in Patients With Hematologic Malignancies

Conditions
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Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Precancerous Condition, Secondary Myelofibrosis

Intervention / Treatment
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* Drug: Busulfan
* Drug: Cytarabine
* Drug: Fludarabine phosphate
* Drug: mycophenolate mofetil
* Drug: tacrolimus
* Procedure: allogeneic hematopoietic stem cell transplantation
* Procedure: umbilical cord blood transplantation
* Radiation: total-body irradiation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of 1 of the following: Acute myeloid leukemia meeting the following criteria: M0-M7 histologic subtypes by French-American-British classification Previously treated disease Meets 1 of the following criteria: Persistent disease as evidenced by 5-30% persistent blasts in bone marrow after induction or salvage therapy In second or subsequent complete remission (CR) In first CR with 1 of the following high-risk features: Philadelphia chromosome present Noncore-binding factor type of chromosomal abnormalities Myelodysplastic syndromes with 1 of the following International Prognostic Scoring System (IPSS) scores: Intermediate-1 Intermediate-2 High-risk score with transfusion dependence Chronic myelogenous leukemia meeting 1 of the following criteria: In accelerated or blastic phase Failed prior imatinib mesylate therapy Acute lymphoblastic leukemia meeting 1 of the following criteria: In first CR with any of the following high-risk features: Philadelphia chromosome present Translocation t(4;11) present WBC > 30,000/mm³ (adult patients) More than 4 weeks from initiation of treatment was required to achieve CR (adult patients) DNA index of near haploid (N=23 chromosomes) (pediatric patients) In second or subsequent CR Persistent disease as evidenced by 5-20% persistent blasts in bone marrow after induction or salvage therapy Hodgkin's or non-Hodgkin's lymphoma meeting the following criteria: Recurrent or refractory disease Tumor ≤ 5 cm in diameter Myeloma or plasma cell neoplasm meeting 1 of the following staging criteria: Stage III at presentation Stage I-II at presentation Not responding OR progressed after first-line therapy Chronic lymphocytic leukemia or Waldenstrom's macroglobulinemia with refractory or progressive disease after first-line therapy No 5-6/6 HLA-matched related or 7-8/8 HLA-matched unrelated marrow or peripheral blood stem cell donor available No single 4-6/6 HLA-A, -B, or -DRB1-matched umbilical cord blood unit ≥ 3.5 x 10^7 nucleated cells/kg available PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 OR Karnofsky or Lansky PS 70-100% Not pregnant Fertile patients must use effective contraception prior to and during study participation HIV negative Bilirubin < 3.0 mg/dL AST and ALT ≤ 3 times upper limit of normal Creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min Cardiac ejection fraction > 50% by echocardiogram OR shortening fraction > 27% No uncontrolled symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia FEV_1 > 50% of normal Forced vital capacity > 50% of normal DLCO normal Oxygen saturation > 92% on room air (for patients < 5 years of age) No history of allergic reactions attributed to compounds of similar chemical or biological composition to busulfan and fludarabine phosphate No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 4 weeks since prior and no concurrent surgery At least 4 weeks since prior and no other concurrent investigational or commercial agents or therapies for the malignancy, including chemotherapy, biologic therapy, or radiotherapy

Ages Eligible for Study
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Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Busulfan|3 mg/kg intravenously over 3 hours|
|Drug: Cytarabine|Patients with previous history of CNS involvement will receive pre-transplant intrathecal Cytarabine (Ara-C) (30 mg/M2) therapy.|
|Drug: Fludarabine phosphate|25 mg/M2/day IV|
|Drug: mycophenolate mofetil|Orally at the dose of 1 gm every 8 hours.|
|Drug: tacrolimus|0.015 mg/kg IV every 12 hours by continuous infusion.|
|Procedure: allogeneic hematopoietic stem cell transplantation|10 days post drug intervention|
|Procedure: umbilical cord blood transplantation|10 days post drug intervention|
|Radiation: total-body irradiation|10 days post drug intervention|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Burkitt lymphoma, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia in remission, recurrent childhood acute lymphoblastic leukemia, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent adult acute myeloid leukemia, adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute promyelocytic leukemia (M3), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), childhood acute myeloblastic leukemia without maturation (M1), childhood acute myeloblastic leukemia with maturation (M2), childhood acute promyelocytic leukemia (M3), childhood acute myelomonocytic leukemia (M4), childhood acute monoblastic leukemia (M5a), childhood acute monocytic leukemia (M5b), childhood acute erythroleukemia (M6), childhood acute megakaryocytic leukemia (M7), childhood acute myeloid leukemia in remission, secondary myelodysplastic syndromes, recurrent childhood acute myeloid leukemia, refractory chronic lymphocytic leukemia, recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, adult grade III lymphomatoid granulomatosis, adult nasal type extranodal NK/T-cell lymphoma, Waldenstrom macroglobulinemia, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent marginal zone lymphoma, secondary acute myeloid leukemia, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, extramedullary plasmacytoma, isolated plasmacytoma of bone, monoclonal gammopathy of undetermined significance, primary systemic amyloidosis, refractory multiple myeloma, de novo myelodysplastic syndromes, childhood acute minimally differentiated myeloid leukemia (M0), childhood grade III lymphomatoid granulomatosis, childhood nasal type extranodal NK/T-cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, recurrent childhood small noncleaved cell lymphoma, previously treated myelodysplastic syndromes, splenic marginal zone lymphoma, recurrent childhood grade III lymphomatoid granulomatosis, recurrent adult lymphoblastic lymphoma, recurrent small lymphocytic lymphoma, secondary myelofibrosis