Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Other Hematologic or Metabolic Diseases

Leukemia Clinical Trial

Official title:

A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Adults and Children With Bone Marrow Failure Syndromes or Inherited Metabolic or Hematologic Diseases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003662
• Other study ID #: CDR0000066755
• Secondary ID: P30CA016056RPCI-
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: March 3, 2011
• Start date: August 1998
• Est. completion date: January 2001

Study information

• Verified date: March 2011
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy or radiation therapy.

PURPOSE: Phase II trial to study the effectiveness of umbilical cord blood transplantation in treating patients who have hematologic cancer or other hematologic or metabolic diseases.

Description:

OBJECTIVES: I. Determine the rates of durable engraftment in patients with severe aplastic anemia, myelodysplastic syndrome, inborn errors of metabolism, or inherited hematopoietic disorders refractory to medical management, who are undergoing high dose chemoradiotherapy followed by unrelated cord blood (UCB) transplantation. II. Determine the incidence and severity of acute and chronic graft-versus-host disease in these patients. III. Monitor overall and event-free survival of these patients. IV. Evaluate rate and quality of immunologic reconstitution of these patients. V. Determine whether nucleated cell or progenitor cell content of the graft is predictive of engraftment.

OUTLINE: This is a multicenter study. Patients are stratified according to low vs high weight. Patients with severe aplastic anemia, myelodysplastic syndrome, or bone marrow failure receive cyclophosphamide IV over 1 hour on days -6 to -3 or melphalan IV over 20 minutes on days -4 to -2, antithymocyte globulin (ATG) IV over 4 hours or methylprednisolone IV over 1 hour twice a day on days -3 to -1, and total lymphoid irradiation on day -1. On day 0, patients receive umbilical cord blood (UCB) infusion. Patients with inborn errors of metabolism or inherited hematopoietic disorders receive oral busulfan every 6 hours on days -9 to -6, cyclophosphamide IV over 1 hour on days -5 to -2 or melphalan IV over 20 minutes on days -4 to -2, and ATG IV over 4 hours or methylprednisolone IV over 1 hour on days -3 to -1. On day 0, patients receive UCB infusion. Patients with Fanconi's anemia receive ATG IV over 4 hours or methylprednisolone IV over 1 hour on days -6 to -1, cyclophosphamide IV over 1 hour on days -5 to -2, thoracoabdominal irradiation on day -1, and then the UCB infusion on day 0. Patients also receive cyclosporine and methylprednisolone beginning on day -2 and continuing as necessary as graft-versus-host disease prophylaxis. Patients are followed indefinitely for survival and late toxicity.

PROJECTED ACCRUAL: A total of 4-90 patients will be accrued for this study within 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: January 2001
• Est. primary completion date: January 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of one of the following: - Severe aplastic anemia with bone marrow cellularity less than 20% and at least 2 of the following criteria: Granulocyte count less than 500/mm3 Platelet count less than 20,000/mm3 Reticulocyte count less than 50,000/mm3 Etiologies may be Fanconi's anemia, hypoplastic leukemia, monosomy 7, drug exposure (chloramphenicol, NSAIDS), viral exposure (EBV, hepatitis, parvovirus, HIV), nutritional deficiencies, thymoma, paroxysmal nocturnal hemoglobinuria, and amegakaryocytic thrombocytopenia - Myelodysplastic syndrome (MDS) that is refractory to medical management or with cytogenetic abnormalities predictive of transformation into acute leukemia, including 5q-, 7q-, monosomy 7, and trisomy 8 De novo primary or therapy-related secondary MDS Refractory anemia or refractory anemia with ringed sideroblasts only - Inherited hematopoietic disorders that are refractory to medical management Severe combined immunodeficiency Familial erythrophagocytic lymphohistiocytosis Wiskott-Aldrich syndrome Kostmann's syndrome (infantile agranulocytosis) Chronic granulomatous disease Leukocyte 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 Lipidoses Must also meet all the following conditions: No HLA-ABC/DR identical related bone marrow or UCB donor No 5/6 antigen matched related bone marrow or UCB donor Condition precludes waiting to search and find a donor in the National Marrow Donor Registry Must have backup autologous or haploidentical related marrow Must have available serologic match umbilical cord blood unit in the New York Blood Center's Placental Blood Project

PATIENT CHARACTERISTICS: Age: Not specified Performance status: Zubrod 0-1 OR Karnofsky or Lansky 80-100% Life expectancy: At least 3 months Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2.0 mg/dL ALT/AST no greater than 4 times normal Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 50 mL/min Cardiovascular: Shortening fraction or ejection fraction at least 80% of normal for age Pulmonary: FVC and FEV1 at least 60% predicted for age Adults: DLCO at least 60% predicted Other: No active concurrent malignancy No active infections at time of backup bone marrow harvest or pretransplant cytoreduction Not pregnant or nursing Negative pregnancy test HIV negative

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome
• Thymic Carcinoma
• Thymoma

Intervention

Biological:
• anti-thymocyte globulin

Drug:
• busulfan

• cyclophosphamide

• cyclosporine

• melphalan

• methylprednisolone

Procedure:
• umbilical cord blood transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	University of South Carolina School of Medicine	Columbia	South Carolina
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	University of Florida Health Science Center	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Division of Pediatric Surgery	Jacksonville	Florida
United States	Children's Hospital of New Orleans	New Orleans	Louisiana
United States	New York Blood Center	New York	New York
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,