Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma

Leukemia

Leukemia, Lymphoid

Anemia

Anemia, Aplastic

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Lymphocytic, Chronic, B-Cell

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Lymphosarcoma

Chronic Graft Versus Host Disease

Aplastic Anemia

Acute Non Lymphoblastic Leukemia

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Fludarabine

Fludarabine phosphate

Melphalan

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Total Body Radiation

Cord Blood

Zachariah DeFilipp, MD

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.

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

Reduced Intensity Double Umbilical Cord Blood Transplantation

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

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.

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.

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.

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.

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

Chronic Graft Versus Host Disease (GVHD) is assessed using the National Institutes of Health (NIH) consensus criteria.

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.

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.

The percentage of participants alive at two years

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.

The number of participants that were found to have lymphoma post-transplant.

Massachusetts General Hospital

Hematology/Oncology

The two participants found to be ineligible after being consented and registered were excluded from the analysis.

All patients receive same therapy

Fludarabine: 30 mg/m2/day IV x 6 days

Melphalan: 100 mg/m2/day IV x 1 day

Total Body Radiation: 200 cGy on Day 0

Cord Blood: 2 cord blood units IV

Fludarabine/Melphalan/TBI

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

Eastern Cooperative Oncology Group (ECOG) Performance Status:

* 0 - Asymptomatic (Fully active, able to carry on all predisease activities without restriction)
* 1 - Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work)
* 2 - Symptomatic, \<50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours)

Performance Status

Disease

Dr. Zachariah DeFilipp

Number of Participants With a Clinically Significant Infection

The two participants found to be ineligible after being consented and registered were excluded from the analysis. In addition to those two participants, the 8 participants that did not achieve engraftment were not included in the analysis.

Median Time to Neutrophil Engraftment

The two participants found to be ineligible after being consented and registered were excluded from the analysis. In addition to those two participants, the 10 participants that did not achieve engraftment were not included in the analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Reduced Intensity Double Umbilical Cord Blood Transplantation	NCT01408563	Non-Hodgkin's L... Hodgkin's Lymph... Multiple Myelom... Chronic Lymphoc... Acute Myelogeno...	Fludarabine Melphalan Total Body Radi... Cord Blood	18 Years - 70 Years	Massachusetts General Hospital
Reduced Intensity Double Umbilical Cord Blood Transplantation	NCT01408563	Non-Hodgkin's L... Hodgkin's Lymph... Multiple Myelom... Chronic Lymphoc... Acute Myelogeno...	Fludarabine Melphalan Total Body Radi... Cord Blood	18 Years - 70 Years	Massachusetts General Hospital

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