Study of Unrelated Cord Blood Transplantation Using Tacrolimus and Sirolimus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00133367
Recruitment Status : Completed
First Posted : August 23, 2005
Last Update Posted : July 25, 2016
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Karen Ballen, Massachusetts General Hospital

Brief Summary:
The purpose of this study is to measure the effectiveness of 2 drugs, tacrolimus and sirolimus, in preventing graft versus host disease (GVHD) after treatment with chemotherapy followed by donor cord blood transplantation.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Non-Hodgkin's Lymphoma Hodgkin's Disease Myelogenous Leukemia Lymphoblastic Leukemia Drug: Tacrolimus Drug: Sirolimus Drug: G-CSF Drug: Antithymocyte globulin Drug: Thymoglobulin Drug: Fludarabine Drug: Melphalan Phase 2

Detailed Description:
  • The chemotherapy portion of the study involves the intravenous administration of fludarabine, for six days (Days 8, 7, 6, 5,4, and 3) before transplant, melphalan, for one day (Day 2) before transplant. Antithymocyte globulin, or thymoglobulin, will be given IV daily for 4 days (days 7, 5, 3, and 1 before transplant). This drug also helps to suppress the immune system, allowing the cord blood cells to grow and reproduce.
  • Immunosuppression therapy consists of the drugs tacrolimus and sirolimus. The patient will receive these 3 days before the transplant and every day for 3-6 months after transplant. After the first 100 days post transplant, the doses of tacrolimus and sirolimus will begin to be reduced with the goal of having the patient off both drugs by 6-9 months after transplant.
  • After completion of conditioning therapy described above, the patient will receive 2 cord blood units 1-6 hours apart. To help with engraftment, the patient will also receive G-CSF starting on day five after transplant, until the patients white blood cells recover.
  • Follow-up visits will continue every 6 months after the last treatment dose and will last up to 2 years.
  • Blood tests will be drawn frequently to test whether the donor's immune cells have engrafted as well as to test the levels of Tacrolimus and Sirolimus.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Sequential Unrelated Cord Blood Transplantation Using Tacrolimus and Sirolimus as Graft Versus Host Disease Prophylaxis
Study Start Date : August 2005
Actual Primary Completion Date : November 2007
Actual Study Completion Date : November 2011

Intervention Details:
  • Drug: Tacrolimus
    Given three days before transplant and every day for 3-6 months after transplant. After first 100 days post-transplant, the dose will be reduced.
  • Drug: Sirolimus
    Given three days before transplant and every day for 3-6 months after transplant. After first 100 days post-transplant, the dose will be reduced.
  • Drug: G-CSF
    Given starting on day 5 after transplant until the subjects white blood cell count recovers.
  • Drug: Antithymocyte globulin
    Given intravenously for 4 days before transplant (days 7, 5, 3, 1).
  • Drug: Thymoglobulin
    Given intravenously for 4 days before transplant (days 7, 5, 3, 1).
  • Drug: Fludarabine
    Given intravenously for six days prior to transplant (days 8,7,6,5,4,3).
  • Drug: Melphalan
    Given intravenously on day 2 before transplant.

Primary Outcome Measures :
  1. To determine the effectiveness of tacrolimus and sirolimus in preventing graft versus host disease [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. To evaluate the days to neutrophil engraftment and platelet engraftment [ Time Frame: 2 years ]
  2. To evaluate the relapse rate and overall disease free survival

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with hematologic malignancies for whom allogeneic stem cell transplantation is deemed clinically appropriate
  • Non-Hodgkin's lymphoma, or Hodgkin's lymphoma: in Complete Remission >2 (second complete remission, third complete remission, etc) or in partial remission
  • Multiple myeloma: relapsed
  • Chronic lymphocytic leukemia, Rai stage III or IV, or lymphocyte doubling time of 6 months, or stage I-II, having progressed after > 2 chemotherapy regimens, in partial remission.
  • Acute myelogenous or lymphoblastic leukemia in second or subsequent remission or in first remission with adverse cytogenetic or antecedent hematologic disorder
  • Chronic myelogenous leukemia in accelerated or second stable phase, or imatinib resistant and not eligible for an ablative transplant
  • Myelodysplasia, previously treated or not eligible for ablative transplant
  • Age 18-65 years.
  • ECOG performance status of 0, 1, or 2.
  • Lack of 6/6 or 5/6 HLA-matched related, 10/10 matched unrelated donor, or unrelated donor not available within the time frame necessary to perform a potentially curative stem cell transplant.

Exclusion Criteria:

  • Cardiac disease:

    • symptomatic congestive heart failure or
    • radionuclide ventriculogram (RVG) or echocardiogram determined left ventricular ejection fraction of < 40%,
    • active angina pectoris, or
    • uncontrolled hypertension.
  • Pulmonary disease:

    • severe chronic obstructive lung disease, or
    • symptomatic restrictive lung disease, or
    • corrected DLCO of < 50% of predicted.
  • Renal disease:

    • serum creatinine > 2.0 mg/dl.
  • Hepatic disease:

    • serum bilirubin > 2.0 mg/dl (except in the case of Gilbert's syndrome or hemolytic anemia in which the bilirubin can be elevated greater than 2.0mg/dl),
    • SGOT or SGPT > 3 x normal.
  • Neurologic disease:

    • symptomatic leukoencephalopathy,
    • active central nervous system (CNS) malignancy or other neuropsychiatric abnormalities believed to preclude transplantation (previous CNS malignancy, presently in complete remission [CR] is not exclusion).
  • HIV antibody.
  • Uncontrolled infection.
  • Pregnancy or breast feeding mother.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00133367

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Principal Investigator: Karen K Ballen, MD Massachusetts General Hospital

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Karen Ballen, Principal Investigator, Massachusetts General Hospital Identifier: NCT00133367     History of Changes
Other Study ID Numbers: 05-154
First Posted: August 23, 2005    Key Record Dates
Last Update Posted: July 25, 2016
Last Verified: July 2016

Keywords provided by Karen Ballen, Massachusetts General Hospital:
Hematologic malignancy
Cord blood transfusion
Graft versus host disease

Additional relevant MeSH terms:
Multiple Myeloma
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Graft vs Host Disease
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lymphatic Diseases
Antilymphocyte Serum