Pilot Study Of Unrelated UCB Transplant for Non-Malignant Hematologic Conditions

NCT00003336 | Completed Phase 2 DMC

• 5 other identifiers: CWRU5Y97P30CA043703CASE-CWRU-5Y97NCI-G98-1431CASE-5Y97
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells. PURPOSE: This phase II trial is studying how well umbilical cord blood transplantation works in treating patients with severe aplastic anemia, malignant thymoma, or myelodysplasia.

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Keywords

refractory anemia; refractory anemia with ringed sideroblasts; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Event-free survival by disease assessment

  at 100 days and at 6, 9, 12, 18, and 24 months

Secondary Outcomes (1)

• Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC) at time of myeloid recovery.

  100 days and at 6, 9, 12, 18, and 24 months

Interventions

anti-thymocyte globulin BIOLOGICAL

The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).

busulfan DRUG

The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).

cyclophosphamide DRUG

The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).

melphalan DRUG

The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).

methylprednisolone DRUG

The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).

bone marrow ablation with stem cell support PROCEDURE

umbilical cord blood transplantation PROCEDURE

One day after the conditioning regimen is completed, patients receive the UCBT.

radiation therapy RADIATION

The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).

Eligibility Criteria

• Age: Up to 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of severe aplastic anemia based on bone marrow cellularity of less than 20% * Must meet at least two of the following criteria: * Granulocyte count less than 500/mm\^3 * Platelet count less than 20,000/mm\^3 * Reticulocyte count less than 50,000/mm\^3 * Following etiologies eligible: * Fanconi's anemia * Hypoplastic leukemia * Monosomy 7 * Drug exposure (chloramphenicol, NSAIDS) * Viral exposure (EBV, hepatitis, parvovirus, HIV) * Nutritional deficiencies * Thymoma * Paroxysmal nocturnal hemoglobinuria * Amegakaryocytic thrombocytopenia OR * Histologically confirmed myelodysplastic syndrome (MDS) that is refractory to medical management or with cytogenic abnormalities predictive of transformation into acute leukemia, including 5q-, 7q-, monosomy 7, or trisomy 8 * The following etiologies only are eligible: * Refractory anemia * Refractory anemia with ringed sideroblasts * De novo primary MDS * Therapy-related secondary MDS OR * Confirmed diagnosis of inherited hematopoietic disorder that is refractory to medical management * Following etiologies eligible: * Severe combined immunodeficiency * Familial erythrophagocytic lymphohistiocytosis * Wiskott-Aldrich syndrome * Kostmann's syndrome (infantile histiocytosis) * Chronic granulomatous disease * Leukocytic adhesion deficiency * Chediak-Higashi syndrome * Paroxysmal nocturnal hemoglobinuria * Fanconi's anemia * Dyskeratosis congenita * Diamond-Blackfan anemia * Amegakaryocytic thrombocytopenia * Osteopetrosis * Gaucher's disease * Lesch-Nyhan syndrome * Mucopolysaccharidoses * Lipodoses * Autologous or haploidentical related peripheral blood stem cells available as backup * Serologically matched umbilical cord blood unit available in the New York Blood Center's Placental Blood Project, or other acceptable umbilical cord blood registry PATIENT CHARACTERISTICS: Age: * 55 and under Performance status: * Zubrod 0-1 * Karnofsky 80-100% Life expectancy: * At least 3 months Hematopoietic: * See Disease Characteristics Hepatic: * ALT/AST no greater than 4 times normal * Bilirubin no greater than 2.0 mg/dL Renal: * Creatinine no greater than 2.0 mg/dL * Creatinine clearance at least 50 mL/min Cardiovascular: * Normal cardiac function by echocardiogram or radionuclide scan * Shortening fraction or ejection fraction at least 80% normal for age * Non-Fanconi patients with acquired or congenital cardiomyopathy may receive melphalan as a substitute for cyclophosphamide Pulmonary: * FVC and FEV\_1 at least 60% of predicted for age * DLCO at least 60% of predicted in adult patients Other: * No active concurrent malignancy * No active infection * Not pregnant or nursing * HIV negative * Must have an available serologic matched Umbilical Cord Blood Unit (UCBU) in the New York Blood Center's Placental Blood Project, or other acceptable Umbilical Cord Blood (UCB) registry PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No concurrent cytotoxic chemotherapy Endocrine therapy: * No concurrent immunosuppressive medications Radiotherapy: * No concurrent radiotherapy Surgery: * Not specified

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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-7284, United States

Location

Related Publications (1)

• Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE, Gerson SL, Lazarus HM, Cairo M, Stevens CE, Rubinstein P, Kurtzberg J. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med. 2001 Jun 14;344(24):1815-22. doi: 10.1056/NEJM200106143442402.

  PMID: 11407342 BACKGROUND

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Anemia, Refractory; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myeloproliferative Disorders

Interventions

Antilymphocyte Serum; Busulfan; Cyclophosphamide; Melphalan; Methylprednisolone; Cord Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; 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; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Mary J. Laughlin, MD

  Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: January 1, 1998
• Primary Completion: December 1, 2005
• Study Completion: February 1, 2006
• Last Updated: June 11, 2010

Record last verified: 2010-06

Locations

US (1)