Clinical trial NCT01408563: Reduced Intensity Double Umbilical Cord Blood Transplantation
Official title: A Phase II Study of Reduced Intensity Double Umbilical Cord Blood Transplantation Using Fludarabine, Melphalan, and Low Dose Total Body Radiation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Multiple Myeloma
Chronic Lymphocytic Leukemia
Acute Myelogenous Leukemia
Keywords: NHL
lymphoma
leukemia
myelodysplastic disorder
aplastic anemia
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-08-03
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With a Clinically Significant Infection
timeFrame: 1 Year
Secondary outcomes:
measure: Median Time to Neutrophil Engraftment
timeFrame: From the time of transplantation, until the time of neutrophil engraftment, median duration of 24 days
measure: Median Time to Platelet Engraftment
timeFrame: From the time of transplantation, until the time of platelet engraftment, median duration of 52 days
measure: Number of Participants With Primary Graft Failure
timeFrame: From the time of transplantation until 42 days post transplantation
measure: Rates of Grade II-IV and Grade III-IV Acute Graft Versus Host Disease (GVHD) at 100 Days
timeFrame: 100 Days
measure: The Rate of Chronic GVHD
timeFrame: From the time of transplantation until the time of chronic GVHD onset, up to 1 year
measure: 100-day Treatment Related Mortality
timeFrame: 100 Days
measure: Immune Reconstitution - Median CD4 Count at 12 Months
timeFrame: 1 Year
measure: Relapse-free Survival
timeFrame: 2 years
measure: Overall Survival
timeFrame: 2 years
measure: 1 Year Relapse Rate
timeFrame: 1 year
measure: Rate of Post-transplant Lymphoma
timeFrame: 2.5 years
measure: Median Thrombopoietin Levels After Transplant
timeFrame: 30 Days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Zachariah DeFilipp, MD
role: PRINCIPAL_INVESTIGATOR
References: