Trial Outcomes & Findings for Reduced Intensity Double Umbilical Cord Blood Transplantation (NCT NCT01408563)

Last Updated: 2019-01-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

1 Year

Results posted on

2019-01-23

Participant Flow

Participant milestones

Participant milestones
Measure	Fludarabine/Melphalan/TBI 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
Overall Study STARTED	33
Overall Study Received Transplant	31
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Fludarabine/Melphalan/TBI 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
Overall Study Ineligible after consent/ registration	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
Age, Continuous	57 years n=31 Participants
Sex: Female, Male Female	9 Participants n=31 Participants
Sex: Female, Male Male	22 Participants n=31 Participants
Region of Enrollment United States	31 Participants n=31 Participants
Performance Status 0	10 Participants n=31 Participants
Performance Status 1	19 Participants n=31 Participants
Performance Status 2	2 Participants n=31 Participants
Disease Acute Lymphoblastic Leukemia (ALL)	2 Participants n=31 Participants
Disease Acute Myeloid Leukemia (AML)	11 Participants n=31 Participants
Disease Hodgkin's Disease (HD)	1 Participants n=31 Participants
Disease Myelodysplastic Syndromes (MDS)	8 Participants n=31 Participants
Disease Myeloproliferative Disorder (MPD)	2 Participants n=31 Participants
Disease Non-Hodgkin Lymphoma (NHL)	7 Participants n=31 Participants

PRIMARY outcome

Timeframe: 1 Year

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

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
Number of Participants With a Clinically Significant Infection 0 Infections	12 Participants
Number of Participants With a Clinically Significant Infection 1 Infection	14 Participants
Number of Participants With a Clinically Significant Infection 2 Infections	5 Participants

SECONDARY outcome

Timeframe: From the time of transplantation, until the time of neutrophil engraftment, median duration of 24 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=23 Participants 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
Median Time to Neutrophil Engraftment	24 Days Interval 1.0 to 54.0

SECONDARY outcome

Timeframe: From the time of transplantation, until the time of platelet engraftment, median duration of 52 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=21 Participants 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
Median Time to Platelet Engraftment	52 Days Interval 21.0 to 89.0

SECONDARY outcome

Timeframe: From the time of transplantation until 42 days post transplantation

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.

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
Number of Participants With Primary Graft Failure	8 Participants

SECONDARY outcome

Timeframe: 100 Days

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

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

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
Rates of Grade II-IV and Grade III-IV Acute Graft Versus Host Disease (GVHD) at 100 Days	16 percentage of participants Interval 5.7 to 31.0

SECONDARY outcome

Timeframe: From the time of transplantation until the time of chronic GVHD onset, up to 1 year

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

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

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
The Rate of Chronic GVHD	21 percentage of participants Interval 8.1 to 37.0

SECONDARY outcome

Timeframe: 100 Days

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

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.

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
100-day Treatment Related Mortality	9.7 percentage of participants Interval 2.4 to 23.0

SECONDARY outcome

Timeframe: 1 Year

Population: CD4 counts were only available for 11 participants at the 12 months time point

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=11 Participants 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
Immune Reconstitution - Median CD4 Count at 12 Months	362.4 cells/mm3 Interval 125.3 to 1157.8

SECONDARY outcome

Timeframe: 2 years

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

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.

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
Relapse-free Survival	49 percentage of participants Interval 30.0 to 66.0

SECONDARY outcome

Timeframe: 2 years

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

The percentage of participants alive at two years

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
Overall Survival	55 percentage of participants Interval 35.0 to 71.0

SECONDARY outcome

Timeframe: 1 year

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.

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
1 Year Relapse Rate	20 percentage Interval 4.0 to 27.3

SECONDARY outcome

Timeframe: 2.5 years

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

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
Rate of Post-transplant Lymphoma	0 Participants

SECONDARY outcome

Timeframe: 30 Days

Outcome measures

Outcome measures
Measure	Fludarabine/Melphalan/TBI n=31 Participants 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
Median Thrombopoietin Levels After Transplant	2500 pg/mL Interval 320.0 to 4000.0

Adverse Events

Fludarabine/Melphalan/TBI

Serious events: 10 serious events

Other events: 26 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Fludarabine/Melphalan/TBI n=31 participants at risk 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
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
General disorders Death NOS	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Nervous system disorders Edema cerebral	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Infections and infestations Encephalitis infection	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Blood and lymphatic system disorders Febrile neutropenia	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
General disorders Fever	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
General disorders General disorders and administration site conditions - Other, specify	3.2% 1/31 • Number of events 2 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Infections and infestations Infections and infestations - Other, specify	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Infections and infestations Lung infection	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Infections and infestations Meningitis	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Gastrointestinal disorders Rectal perforation	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Respiratory, thoracic and mediastinal disorders Respiratory failure	6.5% 2/31 • Number of events 2 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Infections and infestations Sepsis	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Vascular disorders Thromboembolic event	3.2% 1/31 • Number of events 1 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.

Other adverse events

Other adverse events
Measure	Fludarabine/Melphalan/TBI n=31 participants at risk 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
Gastrointestinal disorders Abdominal pain	12.9% 4/31 • Number of events 11 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Metabolism and nutrition disorders Acidosis	6.5% 2/31 • Number of events 3 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Renal and urinary disorders Acute kidney injury	12.9% 4/31 • Number of events 4 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Blood and lymphatic system disorders Anemia	9.7% 3/31 • Number of events 8 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Metabolism and nutrition disorders Anorexia	12.9% 4/31 • Number of events 7 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	19.4% 6/31 • Number of events 21 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Investigations Blood bilirubin increased	9.7% 3/31 • Number of events 3 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Gastrointestinal disorders Colitis	6.5% 2/31 • Number of events 2 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Investigations Creatinine increased	12.9% 4/31 • Number of events 4 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Gastrointestinal disorders Diarrhea	38.7% 12/31 • Number of events 15 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Infections and infestations Encephalitis infection	6.5% 2/31 • Number of events 3 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Blood and lymphatic system disorders Febrile neutropenia	25.8% 8/31 • Number of events 9 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
General disorders Fever	12.9% 4/31 • Number of events 6 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Nervous system disorders Headache	22.6% 7/31 • Number of events 17 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Vascular disorders Hypertension	12.9% 4/31 • Number of events 12 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Metabolism and nutrition disorders Hyperuricemia	6.5% 2/31 • Number of events 2 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Metabolism and nutrition disorders Hypomagnesemia	6.5% 2/31 • Number of events 4 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Metabolism and nutrition disorders Hyponatremia	6.5% 2/31 • Number of events 2 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Vascular disorders Hypotension	9.7% 3/31 • Number of events 3 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.5% 2/31 • Number of events 2 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Infections and infestations Lung infection	6.5% 2/31 • Number of events 3 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Gastrointestinal disorders Mucositis oral	22.6% 7/31 • Number of events 14 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Gastrointestinal disorders Nausea	29.0% 9/31 • Number of events 18 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Investigations Neutrophil count decreased	9.7% 3/31 • Number of events 3 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Investigations Platelet count decreased	19.4% 6/31 • Number of events 16 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.5% 2/31 • Number of events 4 • Adverse events are assessed from the start of treatment until the end of follow-up, up to two years. The two participants found to be ineligible after being consented and registered were excluded from the analysis.

Additional Information

Dr. Zachariah DeFilipp

Massachusetts General Hospital

Phone: 617-643-3944

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place