Umbilical Cord Blood Transplantation From Unrelated Donors

July 17, 2023 updated by: Jane Liesveld, University of Rochester
This study is a single-center, treatment protocol with 4 possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution.

Study Overview

Detailed Description

This study is a single-center treatment protocol with four possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution. Enrolled patients will receive chemotherapy +/-total body radiation as a pre-transplant conditioning regimen. Patients will then receive cord blood stem cells followed by GvHD prophylaxis that will include Tacrolimus and Mycophenolate Mofetil, or Cyclosporin A and Methylprednisolone. Multiple data points will be collected prior to, during, and following transplantation to ensure safety of the process and to evaluate the stated objectives.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 months to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Full Intensity, TBI-based Conditioning
Full Intensity TBI-based Conditioning Total Body Irradiation 1200 cGy in fractions of 150 cGy days -8 or -7 to -4 Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: TBI/Cy
Total Body Irradiation 1200 cGy in 8 fractions
Other Names:
  • TBI 1200 cGy
50 mg/kg or 60 mg/kg
Other Names:
  • Cy
50 mg/kg or 60 mg/kg plus 10% loading dose
Other Names:
  • Pre-Mesna
Intravenous infusion of cord blood stem cells
Other: Full Intensity, Chemo-based Conditioning
Full Intensity, Chemotherapy Conditioning Busulfan days -7 to -4 Recipients <5 years - 1 mg/kg/dose x 16 doses every 6 hours Recipients >/= 5 years - 0.8 mg/kg/dose x 16 doses every 6 hours Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: Bu/Cy
50 mg/kg or 60 mg/kg
Other Names:
  • Cy
50 mg/kg or 60 mg/kg plus 10% loading dose
Other Names:
  • Pre-Mesna
Intravenous infusion of cord blood stem cells
0.8 mg/kg x 16 doses
Other Names:
  • Bu
Other: Reduced Intensity Chemotherapy
Reduced Intensity Chemotherapy Fludarabine 30 mg/m2/day x 5 doses days -6 to -2 Melphalan 140 mg/m2/day x 1 dose day -2 Cord Blood Infusion Other names: Flu/Mel
Intravenous infusion of cord blood stem cells
30 mg/m2/day x 5 or 40 mg/m2/day x 5
Other Names:
  • Flu
140 mg/m2
Other Names:
  • Mel
Other: Non-Myeloablative Conditioning
Fludarabine 40 mg/m2/day x 5 doses days -6 to -2 Cyclophosphamide 50 mg/kg/day x 1 dose day -6 Mesna 50 mg/kg/day with 20% loading dose with Cyclophosphamide dose followed by continuous infusion over 24 hours x 1 dose [to be completed 24 hours after Cyclophosphamide dose] Total Body Irradiation 200 cGy in a single fraction day -1 Cord Blood Infusion Other names: Flu/Cy/TBI
50 mg/kg or 60 mg/kg
Other Names:
  • Cy
50 mg/kg or 60 mg/kg plus 10% loading dose
Other Names:
  • Pre-Mesna
30 mg/m2/day x 5 or 40 mg/m2/day x 5
Other Names:
  • Flu
Total Body Irradiation 200 cGy in one fraction
Other Names:
  • TBI 200 cGy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.]
The date of engraftment of ANC is the first of 3 consecutive days of ANC of 500 or higher based on daily CBC and Differential Counts. The date of engraftment of platelets is the first of three consecutive days of platelet counts of 20,000 or higher in the absence of platelet transfusions for a t least 7 days prior.
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

Outcome Measure
Measure Description
Time Frame
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.
The percentage of patients who fail to initially engraft ANC will be tabulated as well as the percentage of patients who have primary engraftment of ANC but whose graft fails as evidenced by pancytopenia, failure of bone marrow function and loss of donor chimerism following initial engraftment of ANC.
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.
Routine physical exams, liver function tests, and clinical history of diarrhea and upper GI symptoms will be used to assess the presence of, the maximum severity of and the date of onset of Acute GvHD based on the criteria published by Przepioka et al., Bone Marrow Transplant 1995; 15(6):825-8 as used by the Center for International Blood & Marrow Transplant Research. The percentage of patients developing symptoms of acute graft-versus-host disease will be tabulated.
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.
Assess the presence of and the maximum severity of and the date of onset of chronic GvHD based on Sullivan KM, Blood 1981;57-267 as used by the Cneter for International Blood & Marrow Transplant Research.
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.
Document and update the length of time a subject survives without recurrence of the disease for which they were transplanted at 30 days, 100 days, 6 months and yearly following the infusion of cord blood stem cells for as long as the subjects survive and remain disease-free.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jane L Liesveld, MD, Medical Director, Blood & Marrow Transplant Unit

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

December 26, 2016

First Submitted That Met QC Criteria

January 7, 2017

First Posted (Estimated)

January 11, 2017

Study Record Updates

Last Update Posted (Actual)

July 19, 2023

Last Update Submitted That Met QC Criteria

July 17, 2023

Last Verified

July 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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