Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases

November 2, 2023 updated by: Masonic Cancer Center, University of Minnesota

Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for the Treatment of Hematological Diseases

This is a treatment guideline for an unrelated umbilical cord blood transplant (UCBT) using a myeloablative preparative regimen for the treatment of hematological diseases, including, but not limited to acute leukemias. The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a study to collect routine clinical data from UCBT using unrelated single or double UCB units as an alternative, non-HLA-matched stem cell source for patients with hematological diseases.

  • data collection from transplant preparative therapy consisting of treatments with chemotherapeutic regimens and total body irradiation.
  • data collection from umbilical cord blood selection and infusion.
  • data collection from standard supportive disease and transplant related care.

Pre- and post-transplant medication, UCB selection and infusion, supportive care, and follow-up will be according to the current University of Minnesota BMT guidelines.

An average of 18 patients are expected to be treated on this protocol per year.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Not Applicable

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

  • Name: Claudio Brunstein, MD
  • Phone Number: 612-625-3918
  • Email: bruns072@umn.edu

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota Masonic Cancer Center
        • Contact:
        • Principal Investigator:
          • Claudio Brunstein, MD

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

No older than 55 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Eligible Disease Status

    • Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
    • Very high risk pediatric patients with AML: Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
    • Acute Lymphocytic Leukemia (ALL): high risk CR1 as defined by cytogenetics (such as t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
    • Very high risk pediatric patients with ALL: patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
    • Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
    • Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
    • Advanced Myelofibrosis
    • Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia or high risk cytogenetics: Blasts must be < 10% by a representative bone marrow aspirate morphology.
    • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
    • Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy in CR1+ or PR1+.
    • Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
    • Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
    • Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
    • Myeloproliferative Syndromes
  • Availability of suitable UCB unit(s)
  • 0 to 55 years
  • Voluntary written consent (adult or parental/guardian)

Exclusion Criteria:

  • previous irradiation that precludes the safe administration of TBI - Radiation Oncology will evaluate all patients who have had previous radiation therapy
  • chemotherapy refractory large cell and high grade NHL (ie progressive disease after > 2 salvage regimens)
  • if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18 years old prior myeloablative allotransplant or autologous transplant
  • extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
  • pregnant or breastfeeding
  • HIV positive

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Umbilical Cord Blood Transplant
The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.
Drug: Fludarabine
25 mg/m^2 IV of Fludarabine will be given over 1 hour on days -8, -7, and -6 pre-UCB transplant.
Other Names:
  • Fludara
Drug: Cyclophosphamide
60 mg/kg IV of Cyclophosphamide will be given over 2 hours on days -7 and -6 pre-UCB transplant.
Other Names:
  • Cytoxan
Radiation: Total Body Irradiation
165 cGy of total body irradiation will be given twice a day on days -4, -3, -2, and -1.
Drug: Cyclosporine A
Cyclosporine A (CSA) will start day -3 and will be administered PO/IV maintaining a trough level between 200 and 400 ng/mL. For adults the initial dose will be 2.5 mg/kg IV over 1 hour every 12 hours. For children < 40 kg the initial dose will be 2.5 mg/kg IV over 1 hour every 8 hours.
Other Names:
  • CSA
Drug: Mycophenylate mofetil
Mycophenylate mofetil (MMF) 3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. Pediatric patient (<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3.
Other Names:
  • MMF
Biological: Umbilical cord blood
Pre-medications and UCB infusion will be per current institutional policies/guidelines. The infusion of the first UCB unit should begin within 15 minutes, and no later than 30 minutes after arrival on the Unit. If 2 units are used, both cords will be infused within 30-60 minutes of each other as deemed clinically safe by the BMT attending or designee.
Other Names:
  • UCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival at 1 year post-transplant
Time Frame: 1 year
The number of patients that are still living 1 year after UCBT.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of neutrophil engraftment at day 42.
Time Frame: 42 days
Number of subjects with neutrophil engraftment at day 42 post UCBT.
42 days
Platelet engraftment at 1 year.
Time Frame: 1 year
Number of patients with platelet engraftment at 1 year post UCBT.
1 year
Pattern of chimerism after transplant.
Time Frame: 1 year
Pattern of chimerism after transplant. Chimerism will be plotted with box-plots and described over time.
1 year
Incidence of graft failure.
Time Frame: 100 days
Cumulative incidence of graft failure after UCBT.
100 days
Incidence of acute graft versus host disease at 100 days.
Time Frame: 100 days
Cumulative incidence will be used to estimate acute graft versus host disease 100 days after UCBT.
100 days
Incidence of chronic graft versus host disease at 1 year.
Time Frame: 1 year
Cumulative incidence will be used to estimate chronic GVHD at 1 year post UCBT.
1 year
Incidence of transplant related mortality at 6 months.
Time Frame: 6 months
Cumulative incidence will be used to estimate transplant related mortality at 6 months post UCBT.
6 months
Incidence of disease free survival
Time Frame: 1, 2 years
Kaplan-Meier curves will be used to estimate disease-free survival at 1 and 2 years post UCBT.
1, 2 years
Incidence of overall survival.
Time Frame: 1, 2 years
Kaplan-Meier curves will be used to estimate overall survival at 1 and 2 years post UCBT.
1, 2 years

Collaborators and Investigators

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

Sponsor

Masonic Cancer Center, University of Minnesota

Investigators

  • Principal Investigator: Claudio Brunstein, MD, University of Minnesota

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

December 1, 2016

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

October 1, 2025

Study Registration Dates

First Submitted

October 10, 2013

First Submitted That Met QC Criteria

October 10, 2013

First Posted (Estimated)

October 14, 2013

Study Record Updates

Last Update Posted (Actual)

November 3, 2023

Last Update Submitted That Met QC Criteria

November 2, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013OC013

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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