Total Body Irradiation With Fludarabine Followed by Combined Umbilical Cord Blood (UCB) Transplants

NCT00606437 | Completed Phase 1 DMC

• 1 other identifier: Pro00009529
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Results to date of umbilical cord blood transplantation in adult and fully mature adolescent patients are inferior to what is seen in children, due to a lower stem cell dosage in adults and a more toxic conditioning regimen. This phase 1 protocol will use a potentially less toxic bone marrow conditioning regimen, followed by infusion of a combined umbilical cord blood graft that will provide the patient with a higher stem cell dose than can be given with a single umbilical cord blood infusion. The subjects will be conditioned with a total body irradiation (TBI) 13.5 Gy and fludarabine. Following conditioning, up to two unrelated, partially matched umbilical cord blood grafts will be infused that will provide a minimum nucleated cell dose of 3 x 10e7/kg . The primary objective of this study is to measure the frequency of treatment-related toxicity and engraftment.

Conditions

Lymphoma; Myeloma; Leukemia; Myelodysplasia; Solid Tumors; Hodgkin's Disease; Myelofibrosis

Keywords

Umbilical Cord Blood Graft; Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• The primary objective will be to measure the time to and rate of hematologic engraftment following transplant and the frequency of treatment-related mortality.

  3 years

Secondary Outcomes (2)

• The secondary objective will be to estimate the proportion of patients developing acute and chronic graft-versus-host disease, 100 day treatment-related mortality, and to measure disease-free survival.

  3 years

• The tertiary objective will be to measure the time to immunologic reconstitution as defined by normal numbers of T and B cells, normal T-cell proliferative responses, normal natural killer (NK) cell function, and normal immunoglobulin synthesis.

  3 years

Study Arms (1)

I

EXPERIMENTAL

Total Body Irradiation (TBI)/Flu Conditioning followed by combined UCB

Procedure: Total Body Irradiation with Fludarabine in UCB Transplants

Interventions

Total Body Irradiation with Fludarabine in UCB Transplants PROCEDURE

Administration of the preparative regimen, infusion of the stem cell graft, inpatient care during the immediate post-transplant period and outpatient follow-up for the first 3 months after transplant and at 6, 12, 24 and 36 months. Patients will have human leukocyte antigen (HLA) serologic typing and DNA typing. Bags of UCB are thawed, and diluted by 1:1 volume using a 5% albumin/dextran solution. The thawed and diluted umbilical cord blood unit (UCBU) is next weighed and centrifuged. Specimens are obtained for cell count and viability, culture, clonogenic assays, and phenotype. The UCB is infused at a rate of 1-3 ml/min. Furosemide (0.5-1.0 mg/kg/dose) may be given if volume overload or decreased urine output occurs. Each UCB infusion shall be tested for sterility, CFU content, number of CD34+ cells, cell count and viability.

I

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 14 to 65 years.
• Available cord blood graft.
• Patients with high risk ALL in first complete remission, with high risk being defined by the presence of t(4;11), t(9;22) or t(1;19) or patients presenting with extreme hyperleukocytosis (WBC \> 500,000/ul) or partial remission after induction therapy.
• Adult patients with acute non-lymphocytic leukemia (ANLL) in first complete remission with high-risk cytogenetics (monosomy chromosome 5 or 7, del (5q), abn (3q26), complex karyotypic abnormalities) or failure to achieve complete remission after standard induction therapy.
• All patients with ALL or ANLL in second or subsequent remission or partial remission.
• All patients with CML in chronic (failed interferon and/or Gleevec) or accelerated phase.
• Patients with myelodysplastic syndrome with International Prognostic Scoring System (IPSS) risk category of INT-1 or greater.
• Patients with severe aplastic anemia must have failed immunosuppressive therapy such as cyclosporine plus anti-thymocyte globulin.
• Non-Hodgkin's lymphoma or Hodgkin's disease:
• High risk disease in first complete or partial remission
• Chemotherapy-resistant relapse
• Second or subsequent relapse or remission
• Myelofibrosis with myeloid metaplasia.
• High risk, congenital immunodeficiency disorders resulting in recurrent (\> 3 episodes) life-threatening infection, known to be curable with allogeneic stem cell transplantation (to include, but not limited to; severe combined immunodeficiency disorder, combined immunodeficiency disease, Wiskott-Aldrich syndrome, Chediak-Higashi syndrome, chronic granulomatous disease, leukocyte adhesion deficiency, hemophagocytic lymphohistiocytosis).
• Patients with a history of CNS disease must have been treated and have no active CNS disease at the time of protocol treatment.

You may not qualify if:

• Patients that have circulating antibodies specific for donor major histocompatibility antigens (as determined by panel of reactive antibody assay).
• Patients with progressive ANLL or ALL following second or third-line treatment regimens.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Lymphoma; Neoplasms, Plasma Cell; Leukemia; Anemia, Refractory, with Excess of Blasts; Hodgkin Disease; Primary Myelofibrosis

Interventions

Whole-Body Irradiation; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Mitchell Horwitz, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2008
• First Posted: February 4, 2008
• Study Start: September 1, 2005
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: May 16, 2014

Record last verified: 2014-05

Locations

US (1)