Reduced Intensity Double Umbilical Cord Blood Transplantation

Multiple Myeloma Clinical Trial

Official title:

A Phase II Study of Reduced Intensity Double Umbilical Cord Blood Transplantation Using Fludarabine, Melphalan, and Low Dose Total Body Radiation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01408563
• Other study ID #: 11-085
• Status: Completed
• Phase: Phase 2
• Start date: December 2011
• Est. completion date: June 2017

Study information

• Verified date: December 2018
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Chronic Lymphocytic Leukemia
• Hodgkin Disease
• Hodgkin's Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• Fludarabine
30 mg/m2/day IV x 6 days
• Melphalan
100 mg/m2/day IV x 1 day

Radiation:
• Total Body Radiation
200 cGy on Day 0

Biological:
• Cord Blood
2 cord blood units IV

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 Year
Secondary	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.	From the time of transplantation, until the time of neutrophil engraftment, median duration of 24 days
Secondary	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.	From the time of transplantation, until the time of platelet engraftment, median duration of 52 days
Secondary	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.	From the time of transplantation until 42 days post transplantation
Secondary	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	100 Days
Secondary	The Rate of Chronic GVHD	Chronic Graft Versus Host Disease (GVHD) is assessed using the National Institutes of Health (NIH) consensus criteria.	From the time of transplantation until the time of chronic GVHD onset, up to 1 year
Secondary	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.	100 Days
Secondary	Immune Reconstitution - Median CD4 Count at 12 Months		1 Year
Secondary	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.	2 years
Secondary	Overall Survival	The percentage of participants alive at two years	2 years
Secondary	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.	1 year
Secondary	Rate of Post-transplant Lymphoma	The number of participants that were found to have lymphoma post-transplant.	2.5 years
Secondary	Median Thrombopoietin Levels After Transplant		30 Days