Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Nonmalignant Hematologic Disease

This study is currently recruiting patients.

Sponsored by

National Cancer Institute (NCI) 

Fred Hutchinson Cancer Research Center

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Umbilical cord blood transplantation may be able to replace immune cells that were destroyed by the chemotherapy or radiation therapy that was used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of umbilical cord blood transplantation plus combination chemotherapy in treating patients who have hematologic cancer or nonmalignant hematologic disease.

Study Type: Treatment

Official Title: Phase II Study of Unrelated Umbilical Cord Blood Transplantation in Patients with Malignant or Nonmalignant Hematological Disease

Further Study Details: OBJECTIVES: I. Determine the efficacy of umbilical cord blood transplantation, as measured by durable neutrophil engraftment, in patients with malignant or nonmalignant hematological disease. II. Determine the disease free survival and overall survival of these patients. III. Determine the incidence of primary and secondary graft failure, platelet engraftment, and RBC engraftment in these patients after this therapy. IV. Determine the incidence and severity of acute and chronic graft versus host disease, complications (infection, veno-occlusive disease, interstitial pneumonitis), relapse, other malignancies, lymphoproliferative disorders, and posttransplant myelodysplasia in these patients after this therapy. V. Determine the immune reconstitution of these patients after this therapy.  PROTOCOL OUTLINE: This is a multicenter study. Patients are stratified according to disease group (malignant vs nonmalignant). Patients with malignant disease are further stratified according to quality of HLA match (4/6 vs 5/6 or 6/6) and by cell dose. Stratification determines assignment to one of seven groups. Patients receive one of five conditioning regimens, depending on disease. Arm I (malignant disease or severe aplastic anemia): Patients receive total body irradiation (TBI) on days -8 to -4, cyclophosphamide IV on days -3 and -2, and methylprednisolone IV and antithymocyte globulin (ATG) IV on days -3 to -1. Cord blood is transfused on day 0. All males with acute lymphocytic leukemia receive testicular radiotherapy boosts, also. Arm II (Fanconi's anemia): Patients receive cyclophosphamide IV on days -6 to -3 and methylprednisolone IV and ATG IV twice a day on days -5 to -1. Patients receive TBI on day -1. Cord blood is transfused on day 0. Patients then receive ATG IV on days 5, 7, 9, 11, and 13. No testicular boosts are administered. Arm III (inborn errors of metabolism/storage disease): Patients receive oral busulfan every 6 hours on days -6 and -5, cyclophosphamide IV on days -4 and -3, methylprednisolone IV and ATG IV twice a day on days -2 and -1, and TBI on day -1. Cord blood is transfused on day 0. No testicular boosts are administered. Arm IV (other nonmalignant diseases): Patients receive oral busulfan every 6 hours on days -9 to -6, cyclophosphamide IV on days -5 to -2, methylprednisolone IV on days -3 and -2, and ATG IV on days -3 to -1. Patients with familial erythrophagocytic lymphohistiocytosis or Langerhans cell histiocytosis receive etoposide IV on days -5 to -3. Cord blood is transfused on day 0. Arm V (nonTBI regimen for malignant disease, including infant acute lymphocytic leukemia diagnosed at under 1 year and confirmed by 11q23 translocation or MLL gene OR malignant disease and unable to tolerate TBI due to prior dose limiting irradiation): Patients receive oral busulfan every 6 hours on days -8 to -5, melphalan IV on days -4 to -2, and methylprednisolone IV and ATG IV on days -3 to -1. Cord blood is transfused on day 0. All patients receive filgrastim (G-CSF) IV beginning on day 0 and continuing until blood counts recover. Patients are followed weekly for 14 weeks; at 100 days; at 6, 9, and 12 months; every 6 months for 1 year; and then annually thereafter.  PROJECTED ACCRUAL: At least 350 patients will be accrued for this study within 4 years.  

Eligibility

Ages Eligible for Study:  up to   54 Years Criteria

PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Diagnosis of acute myeloid leukemia (AML), with or without myelodysplastic syndrome Not in first complete remission (5% blasts in marrow) with translocations t(8;21) and inv (16) unless failed first line induction therapy Not in first complete remission with translocations t(15;17) abnormality unless: Failed first line induction therapy OR Molecular evidence of persistent disease Not in first complete remission with Down syndrome OR Diagnosis of acute lymphocytic leukemia (ALL) Not in first complete remission OR High risk ALL in first complete remission, with high risk defined as: Hypoploidy (44 chromosomes) OR Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14), except B-cell ALL OR Elevated WBC at presentation 6-12 months old with greater than 100,000/mm3 10-17 years old with greater than 200,000/mm3 18 and over with greater than 20,000/mm3 OR Failed to achieve complete remission after 4 weeks of induction therapy OR Diagnosis of chronic myeloid leukemia Accelerated phase OR Chronic phase if 1 year from diagnosis without matched unrelated bone marrow donor AND unresponsive to or unable to tolerate interferon No blast crisis OR Diagnosis of undifferentiated leukemia (AUL) or biphenotypic leukemia OR Diagnosis of juvenile myelomonocytic leukemia meeting following criteria: No Philadelphia chromosome Bone marrow blasts less than 30% Peripheral blood monocytes greater than 1000/mm3 At least 2 of the following: Peripheral blood spontaneous growth and/or sargramostim (GM-CSF) hypersensitivity Increased hemoglobin F for age Clonal abnormalities (e.g., monosomy 7, RAS mutations) Peripheral blood with myeloid precursors WBC greater than 10,000/mm3 OR Diagnosis of myelodysplastic syndrome defined by the following: Refractory anemia (RA) RA with ringed sideroblasts RA with excess blasts (RAEB) RAEB in transformation Chronic myelomonocytic leukemia Paroxysmal nocturnal hemoglobulinuria OR Diagnosis of Hodgkin's disease or non-Hodgkin's lymphoma beyond first complete reimmission or primary induction failures AND chemosensitive (greater than 50% reduction in tumor mass size) OR Acquired severe aplastic anemia unresponsive to antithymocyte globulin and/or cyclosporine and meeting at least 2 of the following criteria: Granulocyte count less than 500/mm3 Platelet count less than 20,000/mm3 Absolute reticulocyte count less than 20,000/mm3 after correction for hematocrit OR Diagnosis of an inborn error of metabolism including, but not limited to: Hurler's syndrome Adrenoleukodystrophy (ALD) Maroteaux-Lamy syndrome Globoid cell leukodystrophy Metachromatic leukodystrophy Fucosidosis Mannosidosis IQ of 80 required for ALD patients; IQ of 70 for all others OR Fanconi's anemia documented by increased chromosomal fragility assays AND: Severe pancytopenia OR Myelodysplastic syndrome with clonal chromosomal abnormalities OR Leukemic transformation OR Dignosis of combined immune deficiencies including, but not limited to: Severe combined immunodeficiency (SCID) requiring cytoreduction Wiskott-Aldrich syndrome Leukocyte adhesion defect Chediak-Higashi disease X-linked lymphoproliferative disease Adenosine deaminase deficiency Purine nucleoside phosphorylase deficiency X-linked SCID Common variable immune deficiency Nezeloff's syndrome Cartilage hair hypoplasia OR Diagnosis of any of the following: Familial erythrophagocytic lymphohistiocytosis (no positive CSF) Langerhans cell histiocytosis unresponsive to medical management Blackfan-Diamond (congenital pure red cell aplasia) unresponsive to medical therapy Kostmann's congenital agranulocytosis unresponsive to medical therapy Congenital amegakaryocytic thrombocytopenia Infantile osteopetrosis under 2 years of age No dyskeratosis congenita No ALL, AML, AUL, or biphenotypic leukemia, third medullary relpase, or refractory disease other than primary induction failure No active CNS leukemia involvement No consenting 5 of 6 or 6 of 6 HLA matched related donor available --Prior/Concurrent Therapy-- Biologic therapy: At least 12 months since prior allogeneic stem cell transplant with cytoreductive preparative therapy At least 6 months since prior autologous stem cell transplant No concurrent thrombopoietic growth factors Chemotherapy: See Disease Characteristics See Biologic therapy Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified --Patient Characteristics-- Age: Under 55 Performance status: Karnofsky 70-100%, if 16 and over Lansky 50-100%, if under 16 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 2.5 mg/dL SGOT less than 5 times upper limit of normal Renal: Creatinine normal for age OR Creatinine clearance greater than 50% lower limit of normal for age Cardiovascular: If symptomatic, LVEF greater than 40% (or shortening fraction greater than 26%) and improves with exercise Pulmonary: If symptomatic: DLCO, FEV1, and FEC greater than 45% predicted OR Oxygen saturation greater than 85% on room air Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception At least 6 months since proven invasive aspergillosis infection No uncontrolled viral, bacterial, or fungal infection HIV negative No primary myelofibrosis or myelofibrosis of at least grade 3

Location and Contact Information

California

Children's Hospital Los Angeles, Los Angeles,   California,   90027-0700,   United States; Recruiting

Neena Kapoor       213-669-2450   

California

Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,   California,   90095-1781,   United States; Recruiting

Stephen A. Feig       310-825-6708   

Indiana

Indiana University Cancer Center, Indianapolis,   Indiana,   46202-5265,   United States; Recruiting

Franklin O. Smith       317-274-8950   

Maryland

National Heart, Lung, and Blood Institute, Bethesda,   Maryland,   20892,   United States; Recruiting

Lee Ann Jensen       301-435-0066   

Massachusetts

Dana-Farber Cancer Institute, Boston,    Massachusetts,   02115,   United States; Recruiting

Eva Guinan       617-632-4932   

Minnesota

University of Minnesota Medical School, Minneapolis,   Minnesota,   55455,   United States; Recruiting

John E. Wagner, Jr.       612-273-2800   

North Carolina

Duke Comprehensive Cancer Center, Durham,   North Carolina,   27710,   United States; Recruiting

Joanne Kurtzberg       919-668-1100   

Washington

Fred Hutchinson Cancer Research Center, Seattle,   Washington,   98109,   United States; Recruiting

Eric Sievers       206-667-5757   

Study chairs or principal investigators

Lee Ann Jensen,  Study Chair

Fred Hutchinson Cancer Research Center    

More Information

Study ID Numbers  199/14289;   FHCRC-1330.00; NCI-G99-1523

NLM Identifier  NCT00003913

Date study started December 9, 1998

Last Updated  August 1, 1999

Back