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

Sponsor:	Case Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00003336

Purpose

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.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: melphalan Drug: methylprednisolone Procedure: bone marrow ablation with stem cell support Procedure: umbilical cord blood transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With Severe Aplastic Anemia, Inborn Errors in Metabolism, or Inherited Hematologic Stem Cell Disorders

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Anemia Aplastic Anemia Cancer Chronic Myeloid Leukemia Leukemia Myelodysplastic Syndromes

Drug Information available for: Cyclophosphamide Prednisolone Prednisolone acetate Depo-medrol Busulfan Medrol veriderm Methylprednisolone Prednisolone sodium phosphate Melphalan Sarcolysin Prednisolone Sodium Succinate Methylprednisolone Sodium Succinate Methylprednisolone hemisuccinate Melphalan hydrochloride 6-Methylprednisolone

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Event-free survival by disease assessment [ Time Frame: at 100 days and at 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC) at time of myeloid recovery. [ Time Frame: 100 days and at 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]

Enrollment:	6
Study Start Date:	January 1998
Study Completion Date:	February 2006
Primary Completion Date:	December 2005 (Final data collection date for primary outcome measure)

Intervention Details:

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).

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

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).

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.

Eligibility

Ages Eligible for Study:	up to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003336

Locations

United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-7284

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Mary J. Laughlin, MD

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

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Mary J. Laughlin, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00003336 History of Changes
Other Study ID Numbers:	CWRU5Y97, P30CA043703, CASE-CWRU-5Y97, NCI-G98-1431, CASE-5Y97
Study First Received:	November 1, 1999
Last Updated:	June 10, 2010
Health Authority:	United States: Federal Government

Keywords provided by Case Comprehensive Cancer Center:

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

Additional relevant MeSH terms:

Leukemia
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Melphalan
Methylprednisolone Hemisuccinate

Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists

ClinicalTrials.gov processed this record on February 09, 2012