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Study of Unrelated Cord Blood Transplantation Using Tacrolimus and Sirolimus

Primary Purpose

Multiple Myeloma, Non-Hodgkin's Lymphoma, Hodgkin's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tacrolimus
Sirolimus
G-CSF
Antithymocyte globulin
Thymoglobulin
Fludarabine
Melphalan
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Hematologic malignancy, Cord blood transfusion, Graft versus host disease, tacrolimus, sirolimus

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Outcomes

Primary Outcome Measures

To determine the effectiveness of tacrolimus and sirolimus in preventing graft versus host disease

Secondary Outcome Measures

To evaluate the days to neutrophil engraftment and platelet engraftment
To evaluate the relapse rate and overall disease free survival

Full Information

First Posted
August 19, 2005
Last Updated
July 22, 2016
Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00133367
Brief Title
Study of Unrelated Cord Blood Transplantation Using Tacrolimus and Sirolimus
Official Title
Phase II Study of Sequential Unrelated Cord Blood Transplantation Using Tacrolimus and Sirolimus as Graft Versus Host Disease Prophylaxis
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Non-Hodgkin's Lymphoma, Hodgkin's Disease, Myelogenous Leukemia, Lymphoblastic Leukemia
Keywords
Hematologic malignancy, Cord blood transfusion, Graft versus host disease, tacrolimus, sirolimus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
G-CSF
Intervention Description
Given starting on day 5 after transplant until the subjects white blood cell count recovers.
Intervention Type
Drug
Intervention Name(s)
Antithymocyte globulin
Intervention Description
Given intravenously for 4 days before transplant (days 7, 5, 3, 1).
Intervention Type
Drug
Intervention Name(s)
Thymoglobulin
Intervention Description
Given intravenously for 4 days before transplant (days 7, 5, 3, 1).
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Given intravenously for six days prior to transplant (days 8,7,6,5,4,3).
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
Given intravenously on day 2 before transplant.
Primary Outcome Measure Information:
Title
To determine the effectiveness of tacrolimus and sirolimus in preventing graft versus host disease
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To evaluate the days to neutrophil engraftment and platelet engraftment
Time Frame
2 years
Title
To evaluate the relapse rate and overall disease free survival

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen K Ballen, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20107229
Citation
Brown JA, Stevenson K, Kim HT, Cutler C, Ballen K, McDonough S, Reynolds C, Herrera M, Liney D, Ho V, Kao G, Armand P, Koreth J, Alyea E, McAfee S, Attar E, Dey B, Spitzer T, Soiffer R, Ritz J, Antin JH, Boussiotis VA. Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis. Blood. 2010 May 20;115(20):4111-9. doi: 10.1182/blood-2009-09-244145. Epub 2010 Jan 27.
Results Reference
derived

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Study of Unrelated Cord Blood Transplantation Using Tacrolimus and Sirolimus

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