Reduced Intensity Double Umbilical Cord Blood Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Massachusetts General Hospital
Information provided by (Responsible Party):
Karen Ballen, Massachusetts General Hospital Identifier:
First received: August 2, 2011
Last updated: April 6, 2016
Last verified: April 2016

This trial will use two cord blood units for transplantation using a reduced intensity regimen rather than using intense doses of chemotherapy and radiation therapy. Two cord blood units (double cord blood) are being used, as the numbers of blood cells in one unit are too few to allow successful growth of these cells.

Because the risk of infection, particularly virus infection, is high after double cord blood transplant, this study seeks to reduce the rise of virus infection by using a reduced intensity regimen without a medicine called antithymocyte globulin (ATG), as used in prior cord blood transplants. Subjects will receive two chemotherapy drugs, melphalan and fludarabine, and low dose of total body radiation (one treatment) instead of the ATG. The number of patients with virus infections in this study will be compared to our prior experience using the ATG.

Condition Intervention Phase
Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Multiple Myeloma
Chronic Lymphocytic Leukemia
Acute Myelogenous Leukemia
Drug: Fludarabine
Drug: Melphalan
Radiation: Total Body Radiation
Biological: Cord Blood
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Reduced Intensity Double Umbilical Cord Blood Transplantation Using Fludarabine, Melphalan, and Low Dose Total Body Radiation

Resource links provided by NLM:

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • One year significant viral infection rate [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]
    To determine the one year significant viral infection rate (viral infections requiring medical intervention) after double umbilical cord blood transplant using a novel conditioning regimen of fludarabine/melphalan/low dose total body radiation

Secondary Outcome Measures:
  • Time to neutrophil and platelet engraftment [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • Rate of primary graft failure [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • Rates of Grade II-IV and Grade III-IV acute GVHD at 100 days [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • The rate of chronic GVHD [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • 100-day treatment related mortality [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]
  • Immune reconstitution - CD4 count at 12 months [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • Relapse-free and overall survival at 1 and 2 years from transplantation [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • Relapse rate [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • Rate of post-transplant lymphoma [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  • Thrombopoietin levels after transplant [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
    Optional correlate

Estimated Enrollment: 32
Study Start Date: September 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine/Melphalan/TBI
All patients receive same therapy
Drug: Fludarabine
30 mg/m2/day IV x 6 days
Other Name: Fludara
Drug: Melphalan
100 mg/m2/day IV x 1 day
Radiation: Total Body Radiation
200 cGy on Day 0
Biological: Cord Blood
2 cord blood units IV

Detailed Description:

Subjects will receive their transplants as in-patients.

  • IV-Catheter

    • one or two IV catheters will be placed on the day of hospital admission
  • Conditioning

    • Fludarabine IV six days before transplant (days -7, -6, -5. -4, -3, -2)
    • Melphalan IV (day -1)
    • Total body radiation on day 0 (same day as transplant)
  • Immunosuppressive Therapy

    • Tacrolimus and sirolimus beginning day -3, daily for 6-9 months post-transplant. Given IV as in-patient, orally as out-patient
  • Infusion of Cord Blood units

    • 2 cord blood units IV on Day 0 Routine post-transplant supportive care will be provided

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Hematologic malignancy for whom allogeneic stem cell transplantation is deemed clinically appropriate
  • Appropriate candidate for reduced intensity regimen, according to the treating physician
  • Lack of 6/6/ or 5/6 HLA-matched related, 8/8/ HLA-matched unrelated donor, or unrelated donor not available with a time frame necessary to perform a potentially curative stem cell transplant
  • Able to comply with the requirements for care after allogeneic stem cell transplantation

Exclusion Criteria:

  • Cardiac disease: symptomatic congestive heart failure or evidence of left ventricular dysfunction
  • Pulmonary disease: symptomatic chronic obstructive lung disease, symptomatic restrictive lung disease
  • Renal disease
  • Hepatic disease
  • Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation
  • HIV-positive
  • Uncontrolled infection
  • Pregnant or breast-feeding
  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 identifier: NCT01408563

Contact: Karen Ballen, MD 617-724-1121

United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Karen Ballen, MD         
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: David Avigan, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Corey Cutler, MD, MPH         
Sponsors and Collaborators
Massachusetts General Hospital
Principal Investigator: Karen Ballen, MD Massachusetts General Hospital
  More Information

Responsible Party: Karen Ballen, Director, Leukemia, Massachusetts General Hospital Identifier: NCT01408563     History of Changes
Other Study ID Numbers: 11-085 
Study First Received: August 2, 2011
Last Updated: April 6, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
myelodysplastic disorder
aplastic anemia

Additional relevant MeSH terms:
Hodgkin Disease
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma, Non-Hodgkin
Multiple Myeloma
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Vascular Diseases
Fludarabine phosphate
Alkylating Agents
Antimetabolites, Antineoplastic processed this record on May 30, 2016