Umbilical Cord Blood Transplantation From Unrelated Donors

Overview

This study is being done to determine how long it takes for the engraftment (recovery of blood cell counts) of umbilical cord stem cells and also how often engraftment of umbilical cord stem cells transplanted from an unrelated donor fails. Another purpose will be to document the rate of disease-free survival and the rate of relapse (a return of your disease or syndrome) as well as the incidence and severity of graft versus host disease (GvHD) following cord blood stem cell transplantation. GvHD is a complication of stem cell transplants in which white blood cells from the transplanted tissue (graft) attack the transplant recipient's body (host).

Detailed description

PRIMARY OBJECTIVES:

I. Determine the kinetics of engraftment of umbilical cord blood (UCB) following transplantation into unrelated individuals.

II. Determine the incidence of non-engraftment and secondary graft failure when unrelated donor UCB cells are administered to patients receiving myeloablative, reduced intensity cytoreductive, or non-ablative conditioning regimens together with immunosuppressive therapy.

III. Determine the incidence and severity of graft-vs-host disease (GVHD) for patients receiving unrelated donor UCB grafts.

IV. Document the overall survival, disease-free-survival, and rates of relapse for UCB transplant recipients.

OUTLINE: This is an observational study.

Patients undergo a conditioning regimen per standard of care at the discretion of the treating provider, followed by a planned UCB transplantation on study. Patients also have their medical records reviewed for engraftment data on study.

Interventions

• Radiation Total Body Irradiation 1200 cGy
  Total Body Irradiation 1200 cGy in 8 fractions
• Radiation Total Body Irradiation 200 cGy
  Total Body Irradiation 200 cGy in one fraction
• Drug Cyclophosphamide
  50 mg/kg or 60 mg/kg
• Drug Mesna
  50 mg/kg or 60 mg/kg plus 10% loading dose
• Procedure Cord Blood Infusion
  Intravenous infusion of cord blood stem cells
• Drug Busulfan
  0.8 mg/kg x 16 doses
• Drug Fludarabine
  30 mg/m2/day x 5 or 40 mg/m2/day x 5
• Drug Melphalan
  140 mg/m2

Primary outcome measures

• Engraftment of ANC and Platelets [Time frame: 42 days following the infusion of stem cells for ANC [If engraftment of ANC does not occur within 42 days, a subsequent transplant will be performed if a donor is available.]]

Secondary outcome measures (4)

• Rate of non-engraftment and of secondary graft failure [Time frame: At 30 days, 100 days, 6 months and yearly from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.]
• Incidence of acute graft-versus-host disease [Time frame: At 30 days and 100 days after transplant from the date of transplant until the date of documented acute GvHD.]
• Incidence of chronic graft-versus-host disease [Time frame: At 100 days, 6 months and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.]
• Disease-free survival [Time frame: At 30 days, 100 days, 6 months and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.]

Eligibility criteria

Inclusion criteria

• Appropriate diagnosis: Patients must have a disease or syndrome amenable to therapy with hematopoietic stem cell transplantation. Diagnoses include, but are not limited to:
• Congenital and Other Non-malignant Disorders:
• Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome)
• Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta)
• Metabolic disorders (e.g. Hurler's Syndrome)
• Severe aplastic anemia
• High-Risk Leukemia:
• Acute Myelogenous Leukemia
• Refractory to standard induction therapy (more than 1 cycle required to achieve remission)

• Recurrent (in CR ≥ 2)
• Treatment-related AML or MDS
• Evolved from myelodysplastic syndrome
• Presence of FLT3 abnormalities
• FAB M6 or M7
• Adverse cytogenetics
• Myelodysplastic Syndrome
• Acute Lymphoblastic Leukemia including T lymphoblastic leukemia:
• Refractory to standard induction therapy (time to CR >4 weeks)
• Recurrent (in CR ≥ 2)
• WBC count >30,000/mcL at diagnosis
• Age >30 at diagnosis
• Adverse cytogenetics, such as t(9:22), t(1:19), t(4:11), and other MLL rearrangements.
• Chronic Myelogenous Leukemia in accelerated phase or blast crisis
• Biphenotypic or undifferentiated leukemia
• Burkitt's leukemia or lymphoma
• Lymphoma:
• Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemo-sensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous SCT
• Marginal zone or follicular lymphoma that is progressive after at least two prior therapies
• Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible for an autologous HSCT
• Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and disease status
• Adequate organ function:
• Cardiac - LVEF >45%, or shortening fraction >25%, Absence of congestive heart failure or conduction disturbances with high risk for sudden death
• Pulmonary - DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted;
• Renal - serum Cr < 1.5 times the upper limit of normal for age or GFR ≥ 50 ml/min/1.73m2
• Hepatic - total bilirubin level < 2 times the upper limit of normal (except for patients with Gilbert's syndrome or hemolysis); if the primary disease process is causal, this criterion will be reconsidered. ALT, AST, and Alkaline phosphatase ≤ 5 times upper limit of normal.
• Performance Status Karnofsky or Lansky score ≥ 70%.
• Informed Consent must be obtained prior to initiating conditioning therapy.
• Receipt of viable cord blood product(s), single or dual, must be confirmed with the stem cell processing laboratory prior to initiating conditioning therapy.

Exclusion criteria

• Availability of 10/10 or 9/10 HLA-matched related or unrelated donor within a reasonable timeframe dictated by the clinical urgency of the transplant
• Autologous HSCT < 6 months prior to proposed UCB transplant
• Pregnant or breast feeding
• Current uncontrolled infection
• Evidence of HIV infection or positive HIV serology

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• Wilmot Cancer Institute — Rochester

Identifiers

NCT: NCT03016806 · UBMT 15029

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗