Clinical trial NCT00133367: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2005-08-23
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To determine the effectiveness of tacrolimus and sirolimus in preventing graft versus host disease
timeFrame: 2 years
Secondary outcomes:
measure: To evaluate the days to neutrophil engraftment and platelet engraftment
timeFrame: 2 years
measure: To evaluate the relapse rate and overall disease free survival
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Karen K Ballen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.