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

NCT ID: NCT00003336

Last Updated: 2010-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-01-31
• Study Completion Date: 2006-02-28

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.

Detailed Description

OBJECTIVES:

• 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.
• Evaluate the rate and quality of immunologic reconstitution in this patient population.

OUTLINE: Patients are stratified according to weight (under 45 kg vs over 45 kg).

Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT). The regimen varies according to the underlying cause of the anemia, but could include busulfan, cyclophosphamide or melphalan, anti-thymocyte globulin or methylprednisolone, and/or radiation therapy. One day after the conditioning regimen is completed, patients receive the UCBT.

Patients are followed weekly for 3 months, at 6 months, then every 6 months for 2.5 years, then annually thereafter.

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

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

anti-thymocyte globulin

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).

Intervention Type: BIOLOGICAL

busulfan

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).

Intervention Type: DRUG

cyclophosphamide

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).

Intervention Type: DRUG

melphalan

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).

Intervention Type: DRUG

methylprednisolone

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).

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

umbilical cord blood transplantation

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

Intervention Type: PROCEDURE

radiation therapy

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).

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

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

Principal Investigators

Mary J. Laughlin, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Cleveland, Ohio, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 11407342 (View on PubMed)

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE-CWRU-5Y97

Identifier Type: -

Identifier Source: secondary_id

NCI-G98-1431

Identifier Type: -

Identifier Source: secondary_id

CASE-5Y97

Identifier Type: -

Identifier Source: secondary_id

CWRU5Y97

Identifier Type: -

Identifier Source: org_study_id