Donor Umbilical Cord Blood Transplantation in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders

NCT00055653 | Completed Phase 2 DMC

• 2 other identifiers: CDR0000270487RPCI-DS-00-22
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 25

Brief Summary

RATIONALE: 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 allogeneic umbilical cord blood transplantation in treating patients who have leukemia, lymphoma, or nonmalignant hematologic disorders.

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases

Keywords

refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory anemia; chronic myelomonocytic leukemia; childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; childhood acute lymphoblastic leukemia in remission; recurrent childhood acute lymphoblastic leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; acute undifferentiated leukemia; recurrent/refractory childhood Hodgkin lymphoma; recurrent childhood large cell lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent childhood small noncleaved cell lymphoma; untreated childhood acute lymphoblastic leukemia; untreated childhood acute myeloid leukemia and other myeloid malignancies; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable

Interventions

anti-thymocyte globulin BIOLOGICAL

filgrastim BIOLOGICAL

busulfan DRUG

cyclophosphamide DRUG

cyclosporine DRUG

fludarabine phosphate DRUG

melphalan DRUG

methylprednisolone DRUG

umbilical cord blood transplantation PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following hematologic malignancies: * Acute myeloid leukemia (AML)\* * With or without history of myelodysplastic syndromes (MDS) * Patients in first complete remission (CR) (no greater than 5% blasts in marrow) with translocations t(8;21) and inv(16) are allowed provided they failed first-line induction therapy * Patients in first CR (no greater than 5% blasts in marrow) with translocations t(15;17) are allowed provided at least 1 of the following is true: * Failed first-line induction therapy * Molecular evidence of persistent disease * No patients in first CR and with Down syndrome * Acute lymphoblastic leukemia (ALL)\*, meeting 1 of the following criteria: * Not in first CR (no greater than 5% blasts in marrow) * In first CR and high risk as defined by 1 of the following: * Hypoploidy (no more than 44 chromosomes) * Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14) (excluding B-ALL) or +MLL gene rearrangement * One of the following elevated WBC levels: * WBC greater than 100,000/mm\^3 if 6 to 12 months of age * WBC greater than 200,000/mm\^3 if between 10 and 17 years of age * WBC greater than 20,000/mm\^3 if 18 years of age and over (adult \[over 18 years of age\] patient stratum closed to accrual) * Failed to achieve CR after 4 weeks of induction therapy * B-ALL that is not in first CR or that meets at least 1 of the high-risk criteria specified above * No translocation t(8;14) * No blasts with surface immunoglobulins * CD10 negative * Undifferentiated leukemia\* * Infant leukemia\* * Biphenotypic leukemia\* * Chronic myelogenous leukemia, meeting 1 of the following criteria: * Accelerated phase * Chronic phase * At least 1 year from diagnosis without an identified matched unrelated bone marrow donor AND unresponsive to or unable to tolerate interferon * Blast crisis\* (greater than 30% promyelocytes plus blasts in the marrow) * One of the following MDS: * Refractory anemia * Refractory anemia with ringed sideroblasts * Refractory anemia with excess blasts (RAEB) * RAEB in transformation * Chronic myelomonocytic leukemia * Paroxysmal nocturnal hemoglobinuria * Hodgkin's or non-Hodgkin's lymphoma beyond first CR or failed primary induction therapy * Tumor displays chemosensitivity (greater than 50% reduction in mass size after the most recent therapy) NOTE: \*Patients in third or greater medullary relapse or refractory disease (other than primary induction failures) or blast crisis receive the study busulfan/melphalan conditioning regimen) OR * Diagnosis of one of the following nonmalignant diseases : * Acquired severe aplastic anemia (stratum closed to accrual) * Unresponsive to medical therapy with anti-thymocyte globulin and/or cyclosporine * Inborn errors of metabolism, including, but not limited to the following: * Hurler's syndrome * Adrenoleukodystrophy * Maroteaux-Lamy syndrome * Globoid cell leukodystrophy * Metachromatic leukodystrophy * Fucosidosis * Mannosidosis * Fanconi anemia documented by increased chromosomal fragility assays and meeting 1 of the following criteria (stratum closed to accrual): * Severe pancytopenia * Absolute neutrophil count less than 500/mm\^3 * Platelet count less than 20,000/mm\^3 * Hemoglobin less than 8 g/dL * Morphologic evidence of MDS with clonal chromosomal abnormalities * Leukemia transformation * Other marrow failure syndromes, including any of the following (stratum closed to accrual): * Blackfan-Diamond syndrome that is unresponsive to medical therapy * Kostmann's congenital agranulocytosis unresponsive to medical therapy * Congenital amegakaryocytic thrombocytopenia * Thrombocytopenia absent radius * Combined immune deficiencies including, but not limited to the following: * Severe combined immunodeficiency (SCID) * 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 * Reticular dysgenesis * No active CNS leukemia (cerebrospinal fluid with WBC greater than 5/mm\^3 and malignant cells on cytospin) * No SCID patients who do not require cytoreduction * No dyskeratosis congenita * No primary myelofibrosis * No grade 3 or greater myelofibrosis * Familial erythrophagocytic lymphohistiocytosis patients must not have any of the following: * Abnormal brain MRI * Neurologic symptoms * Lymphocytes and monocytes greater than 7/mm\^3 in the cerebrospinal fluid * No available 5/6 or 6/6 HLA-matched related donor PATIENT CHARACTERISTICS: Age * 55 and under (over 18 closed to accrual) Performance status * Karnofsky 70-100% OR * Lansky 50-100% (patients under 16 years old) Life expectancy * Not specified Hematopoietic * See Disease Characteristics Hepatic * SGOT less than 5 times upper limit of normal * Bilirubin less than 2.5 mg/dL Renal * Creatinine normal for age OR * Creatinine clearance or glomerular filtration rate greater than 50% of lower limit of normal Cardiovascular * LVEF greater than 40% at rest and must improve with exercise\* OR * Shortening fraction greater than 26%\* NOTE: \*If symptomatic Pulmonary * DLCO greater than 45% of predicted\* (corrected for hemoglobin) * FEV\_1 and FEC greater than 45% of predicted (corrected for hemoglobin) OR * Room air oxygen saturation greater than 85%\* NOTE: \*If symptomatic Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No uncontrolled viral, bacterial, or fungal infection * HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * More than 12 months since prior allogeneic stem cell transplantation with cytoreductive preparative therapy * More than 6 months since prior autologous stem cell transplantation Chemotherapy * See Biologic therapy Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified Other * No prior enrollment on this study * No continuous life support (e.g., mechanical ventilation) within 1 year after study transplantation (for patients with inborn errors of metabolism)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (25)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, 90095-1781, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Children's Medical Center, University of California San Francisco

San Francisco, California, 94143-1278, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Children's Hospital of New Orleans

New Orleans, Louisiana, 70118, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Spectrum Health and DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104-1095, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Ireland Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6310, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

Children's Medical Center of Dallas

Dallas, Texas, 75235, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory; Leukemia, Myelomonocytic, Chronic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Leukemia, Myeloid, Chronic-Phase; Leukemia, Biphenotypic, Acute; Recurrence; Dendritic Cell Sarcoma, Interdigitating; Burkitt Lymphoma; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myeloproliferative Disorders

Interventions

Antilymphocyte Serum; Filgrastim; Busulfan; Cyclophosphamide; Cyclosporine; fludarabine phosphate; Melphalan; Methylprednisolone; Cord Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Anemia; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Histiocytic Disorders, Malignant; Histiocytosis; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Philip L. McCarthy, MD

  Roswell Park Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 6, 2003
• First Posted: March 7, 2003
• Study Start: January 1, 2003
• Primary Completion: September 1, 2003
• Study Completion: September 1, 2005
• Last Updated: March 7, 2011

Record last verified: 2011-03

Locations

US (25)