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Reduced Intensity Double Umbilical Cord Blood Transplantation

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Melphalan
Total Body Radiation
Cord Blood
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma focused on measuring NHL, lymphoma, leukemia, myelodysplastic disorder, aplastic anemia

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fludarabine/Melphalan/TBI

Arm Description

All patients receive same therapy

Outcomes

Primary Outcome Measures

Number of Participants With a Clinically Significant Infection
The one year significant infection rate (infections requiring medical intervention) after double umbilical cord blood transplant using a novel conditioning regimen of fludarabine/melphalan/low dose total body radiation. The data is shown as the number of significant infections participants experienced during the first year, measured from the start of treatment.

Secondary Outcome Measures

Median Time to Neutrophil Engraftment
The median number of days measured from the time of transplantation, until the first documented neutrophil engraftment. neutrophil engraftment is defined as the first of 3 consecutive days of absolute neutrophil count > 500 neutrophils per microliter of blood.
Median Time to Platelet Engraftment
The time to platelet engraftment is measured from the time of transplantation until the time of first documented platelet engraftment. Platelet engraftment is defined as a platelet count ≥ 20,000/µL for three consecutive measurements over three or more days. The first of the three days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 3 days or in the following 7 days after the day of engraftment, unless the platelet transfusion is being given specifically to achieve a platelet threshold to allow an elective invasive procedure, such as a central catheter removal.
Number of Participants With Primary Graft Failure
Primary graft failure is defined as the failure to achieve an absolute neutrophil count (ANC) >500/ µL by day 42, in the absence of relapse.
Rates of Grade II-IV and Grade III-IV Acute Graft Versus Host Disease (GVHD) at 100 Days
Acute GVHD is assessed using Consensus Criteria: Organ Classifications: 0: No rash due to GVHD; Bilirubin < 2 mg/dL; < 500 mL diarrhea/ day 1: Maculopapular rash < 25% of body surface; Bilirubin 2-3 mg/dL; 500 to 999 mL diarrhea/ day or persistent nausea with histologic evidence of GVHD in stomach/ duodenum 2: Maculopapular rash 25-50% of body surface; Bilirubin 3.1-6 mg/dL; 1,000 to 1,499 mL diarrhea/ day 3: Maculopapular rash > 50% of body surface; Bilirubin 6.1-15 mg/dL; 1,500 or more mL diarrhea/ day 4: Generalized erythroderma with bullous formation; Bilirubin > 15 mg/dL; Severe abdominal pain with or without ileus Overall Clinical Grade: 0: No Stage 1-4 of any organ I: Stage 1-2 rash and no liver or gut involvement II: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 gut involvement III: None to Stage 3 skin rash with Stage 2-3 liver involvement, or Stage 2-4 gut involvement IV: Stage 4 skin rash, or Stage 4 liver involvement
The Rate of Chronic GVHD
Chronic Graft Versus Host Disease (GVHD) is assessed using the National Institutes of Health (NIH) consensus criteria.
100-day Treatment Related Mortality
The percentage of treatment related participant deaths within 100 days of receiving umbilical cord blood transplantation. All deaths in the absence of relapse of the primary malignancy will be considered treatment related mortality.
Immune Reconstitution - Median CD4 Count at 12 Months
Relapse-free Survival
The percentage of participants that have not died or had disease progression by two years. Relapse is defined by either morphological or cytogenetic evidence of the original malignancy consistent with pre-transplant features.
Overall Survival
The percentage of participants alive at two years
1 Year Relapse Rate
The percentage of participants that relapsed within 12 months. Relapse is defined by either morphological or cytogenetic evidence of the original malignancy consistent with pre-transplant features.
Rate of Post-transplant Lymphoma
The number of participants that were found to have lymphoma post-transplant.
Median Thrombopoietin Levels After Transplant

Full Information

First Posted
August 2, 2011
Last Updated
December 29, 2018
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01408563
Brief Title
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

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Chronic Lymphocytic Leukemia, Acute Myelogenous Leukemia
Keywords
NHL, lymphoma, leukemia, myelodysplastic disorder, aplastic anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fludarabine/Melphalan/TBI
Arm Type
Experimental
Arm Description
All patients receive same therapy
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
30 mg/m2/day IV x 6 days
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
100 mg/m2/day IV x 1 day
Intervention Type
Radiation
Intervention Name(s)
Total Body Radiation
Intervention Description
200 cGy on Day 0
Intervention Type
Biological
Intervention Name(s)
Cord Blood
Intervention Description
2 cord blood units IV
Primary Outcome Measure Information:
Title
Number of Participants With a Clinically Significant Infection
Description
The one year significant infection rate (infections requiring medical intervention) after double umbilical cord blood transplant using a novel conditioning regimen of fludarabine/melphalan/low dose total body radiation. The data is shown as the number of significant infections participants experienced during the first year, measured from the start of treatment.
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Median Time to Neutrophil Engraftment
Description
The median number of days measured from the time of transplantation, until the first documented neutrophil engraftment. neutrophil engraftment is defined as the first of 3 consecutive days of absolute neutrophil count > 500 neutrophils per microliter of blood.
Time Frame
From the time of transplantation, until the time of neutrophil engraftment, median duration of 24 days
Title
Median Time to Platelet Engraftment
Description
The time to platelet engraftment is measured from the time of transplantation until the time of first documented platelet engraftment. Platelet engraftment is defined as a platelet count ≥ 20,000/µL for three consecutive measurements over three or more days. The first of the three days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 3 days or in the following 7 days after the day of engraftment, unless the platelet transfusion is being given specifically to achieve a platelet threshold to allow an elective invasive procedure, such as a central catheter removal.
Time Frame
From the time of transplantation, until the time of platelet engraftment, median duration of 52 days
Title
Number of Participants With Primary Graft Failure
Description
Primary graft failure is defined as the failure to achieve an absolute neutrophil count (ANC) >500/ µL by day 42, in the absence of relapse.
Time Frame
From the time of transplantation until 42 days post transplantation
Title
Rates of Grade II-IV and Grade III-IV Acute Graft Versus Host Disease (GVHD) at 100 Days
Description
Acute GVHD is assessed using Consensus Criteria: Organ Classifications: 0: No rash due to GVHD; Bilirubin < 2 mg/dL; < 500 mL diarrhea/ day 1: Maculopapular rash < 25% of body surface; Bilirubin 2-3 mg/dL; 500 to 999 mL diarrhea/ day or persistent nausea with histologic evidence of GVHD in stomach/ duodenum 2: Maculopapular rash 25-50% of body surface; Bilirubin 3.1-6 mg/dL; 1,000 to 1,499 mL diarrhea/ day 3: Maculopapular rash > 50% of body surface; Bilirubin 6.1-15 mg/dL; 1,500 or more mL diarrhea/ day 4: Generalized erythroderma with bullous formation; Bilirubin > 15 mg/dL; Severe abdominal pain with or without ileus Overall Clinical Grade: 0: No Stage 1-4 of any organ I: Stage 1-2 rash and no liver or gut involvement II: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 gut involvement III: None to Stage 3 skin rash with Stage 2-3 liver involvement, or Stage 2-4 gut involvement IV: Stage 4 skin rash, or Stage 4 liver involvement
Time Frame
100 Days
Title
The Rate of Chronic GVHD
Description
Chronic Graft Versus Host Disease (GVHD) is assessed using the National Institutes of Health (NIH) consensus criteria.
Time Frame
From the time of transplantation until the time of chronic GVHD onset, up to 1 year
Title
100-day Treatment Related Mortality
Description
The percentage of treatment related participant deaths within 100 days of receiving umbilical cord blood transplantation. All deaths in the absence of relapse of the primary malignancy will be considered treatment related mortality.
Time Frame
100 Days
Title
Immune Reconstitution - Median CD4 Count at 12 Months
Time Frame
1 Year
Title
Relapse-free Survival
Description
The percentage of participants that have not died or had disease progression by two years. Relapse is defined by either morphological or cytogenetic evidence of the original malignancy consistent with pre-transplant features.
Time Frame
2 years
Title
Overall Survival
Description
The percentage of participants alive at two years
Time Frame
2 years
Title
1 Year Relapse Rate
Description
The percentage of participants that relapsed within 12 months. Relapse is defined by either morphological or cytogenetic evidence of the original malignancy consistent with pre-transplant features.
Time Frame
1 year
Title
Rate of Post-transplant Lymphoma
Description
The number of participants that were found to have lymphoma post-transplant.
Time Frame
2.5 years
Title
Median Thrombopoietin Levels After Transplant
Time Frame
30 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zachariah DeFilipp, 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
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

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Reduced Intensity Double Umbilical Cord Blood Transplantation

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