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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01962636
First received: October 10, 2013
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention
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
Drug: Fludarabine
Drug: Cyclophosphamide
Radiation: Total Body Irradiation
Drug: Cyclosporine A
Drug: Mycophenylate mofetil
Biological: Umbilical cord blood

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for the Treatment of Hematological Diseases

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Survival at 1 year post-transplant [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    The number of patients that are still living 1 year after UCBT.


Secondary Outcome Measures:
  • Incidence of neutrophil engraftment at day 42. [ Time Frame: 42 days ] [ Designated as safety issue: No ]
    Number of subjects with neutrophil engraftment at day 42 post UCBT.

  • Platelet engraftment at 1 year. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Number of patients with platelet engraftment at 1 year post UCBT.

  • Pattern of chimerism after transplant. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Pattern of chimerism after transplant. Chimerism will be plotted with box-plots and described over time.

  • Incidence of graft failure. [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    Cumulative incidence of graft failure after UCBT.

  • Incidence of acute graft versus host disease at 100 days. [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Cumulative incidence will be used to estimate chronic GVHD at 1 year post UCBT.

  • Incidence of transplant related mortality at 6 months. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Cumulative incidence will be used to estimate transplant related mortality at 6 months post UCBT.

  • Incidence of disease free survival [ Time Frame: 1, 2 years ] [ Designated as safety issue: Yes ]
    Kaplan-Meier curves will be used to estimate disease-free survival at 1 and 2 years post UCBT.

  • Incidence of overall survival. [ Time Frame: 1, 2 years ] [ Designated as safety issue: Yes ]
    Kaplan-Meier curves will be used to estimate overall survival at 1 and 2 years post UCBT.


Estimated Enrollment: 200
Study Start Date: May 2014
Estimated Study Completion Date: October 2023
Estimated Primary Completion Date: October 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Fludara
Drug: Cyclophosphamide
60 mg/kg IV of Cyclophosphamide will be given over 2 hours on days -7 and -6 pre-UCB transplant.
Other Name: 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 Name: 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 Name: 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 Name: UCB

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.

  Eligibility

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01962636

Contacts
Contact: Claudio Brunstein, MD 612-625-3918 bruns072@umn.edu

Locations
United States, Minnesota
University of Minnesota Masonic Cancer Center Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Claudio Brunstein, MD    612-625-3918    bruns072@umn.edu   
Principal Investigator: Claudio Brunstein, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Claudio Brunstein, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01962636     History of Changes
Other Study ID Numbers: 2013OC013
Study First Received: October 10, 2013
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
Plasma Cell Leukemia
Umbilical Cord Transplant
Acute Myeloid Leukemia (AML)
Acute Lymphocytic Leukemia (ALL)
Chronic Myelogenous 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

Additional relevant MeSH terms:
Leukemia, Plasma Cell
Burkitt Lymphoma
Hematologic Diseases
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Prolymphocytic
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Multiple Myeloma
Myelodysplastic Syndromes
Neoplasms, Plasma Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Primary Myelofibrosis
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
DNA Virus Infections
Epstein-Barr Virus Infections
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on October 30, 2014