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

Primary Purpose

Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Cyclophosphamide
Total Body Irradiation
Cyclosporine A
Mycophenylate mofetil
Umbilical cord blood
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Umbilical Cord Transplant, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia, Plasma Cell Leukemia, Myelofibrosis, Myelodysplasia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, Large Cell Non-Hodgkin Lymphoma, Lymphoblastic Lymphoma, Burkitt's Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma

Eligibility Criteria

undefined - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Minnesota Masonic Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Umbilical Cord Blood Transplant

Arm Description

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.

Outcomes

Primary Outcome Measures

Survival at 1 year post-transplant
The number of patients that are still living 1 year after UCBT.

Secondary Outcome Measures

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

Full Information

First Posted
October 10, 2013
Last Updated
November 2, 2022
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT01962636
Brief Title
Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases
Official Title
Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for the Treatment of Hematological Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 2016 (undefined)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia, Plasma Cell Leukemia, Myelofibrosis, Myelodysplasia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, Diffuse Large B Cell Lymphoma, Lymphoblastic Lymphoma, Burkitt's Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma
Keywords
Umbilical Cord Transplant, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia, Plasma Cell Leukemia, Myelofibrosis, Myelodysplasia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, Large Cell Non-Hodgkin Lymphoma, Lymphoblastic Lymphoma, Burkitt's Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Umbilical Cord Blood Transplant
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
25 mg/m^2 IV of Fludarabine will be given over 1 hour on days -8, -7, and -6 pre-UCB transplant.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
60 mg/kg IV of Cyclophosphamide will be given over 2 hours on days -7 and -6 pre-UCB transplant.
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Intervention Description
165 cGy of total body irradiation will be given twice a day on days -4, -3, -2, and -1.
Intervention Type
Drug
Intervention Name(s)
Cyclosporine A
Other Intervention Name(s)
CSA
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Mycophenylate mofetil
Other Intervention Name(s)
MMF
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Umbilical cord blood
Other Intervention Name(s)
UCB
Intervention Description
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.
Primary Outcome Measure Information:
Title
Survival at 1 year post-transplant
Description
The number of patients that are still living 1 year after UCBT.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Incidence of neutrophil engraftment at day 42.
Description
Number of subjects with neutrophil engraftment at day 42 post UCBT.
Time Frame
42 days
Title
Platelet engraftment at 1 year.
Description
Number of patients with platelet engraftment at 1 year post UCBT.
Time Frame
1 year
Title
Pattern of chimerism after transplant.
Description
Pattern of chimerism after transplant. Chimerism will be plotted with box-plots and described over time.
Time Frame
1 year
Title
Incidence of graft failure.
Description
Cumulative incidence of graft failure after UCBT.
Time Frame
100 days
Title
Incidence of acute graft versus host disease at 100 days.
Description
Cumulative incidence will be used to estimate acute graft versus host disease 100 days after UCBT.
Time Frame
100 days
Title
Incidence of chronic graft versus host disease at 1 year.
Description
Cumulative incidence will be used to estimate chronic GVHD at 1 year post UCBT.
Time Frame
1 year
Title
Incidence of transplant related mortality at 6 months.
Description
Cumulative incidence will be used to estimate transplant related mortality at 6 months post UCBT.
Time Frame
6 months
Title
Incidence of disease free survival
Description
Kaplan-Meier curves will be used to estimate disease-free survival at 1 and 2 years post UCBT.
Time Frame
1, 2 years
Title
Incidence of overall survival.
Description
Kaplan-Meier curves will be used to estimate overall survival at 1 and 2 years post UCBT.
Time Frame
1, 2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Claudio Brunstein, MD
Phone
612-625-3918
Email
bruns072@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudio Brunstein, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota Masonic Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudio Brunstein, MD
Phone
612-625-3918
Email
bruns072@umn.edu
First Name & Middle Initial & Last Name & Degree
Claudio Brunstein, MD

12. IPD Sharing Statement

Learn more about this trial

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

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