Trial Outcomes & Findings for Myeloablative Umbilical Cord Blood Transplantation in Hematological Diseases (NCT NCT00309842)

NCT ID: NCT00309842

Last Updated: 2020-09-10

Results Overview

Number of patients alive at 1 year after transplant.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 213 participants
• Primary outcome timeframe: at 1 year
• Results posted on: 2020-09-10

Participant Flow

Participant milestones

Measure	Unrelated UCBT for Blood Cancers Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Overall Study STARTED	213
Overall Study COMPLETED	212
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Unrelated UCBT for Blood Cancers Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Overall Study Lost to Follow-up	1

Baseline Characteristics

Myeloablative Umbilical Cord Blood Transplantation in Hematological Diseases

Baseline characteristics by cohort

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Age, Categorical <=18 years	76 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	136 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	96 Participants n=5 Participants
Sex: Female, Male Male	116 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	199 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	13 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants
Race (NIH/OMB) White	162 Participants n=5 Participants
Race (NIH/OMB) More than one race	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: at 1 year

Number of patients alive at 1 year after transplant.

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Number of Participants Who Were Alive at 1 Year Transplant Overall Survival	130 Participants

SECONDARY outcome

Timeframe: At Month 6

Determine the incidence of transplant-related mortality at 6 months after UCBT

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Number of Participants Who Died Due to Transplant	58 Participants

SECONDARY outcome

Timeframe: 6 months

Determine the incidence of platelet engraftment (platelet recovery >50,000/uL) at 6 months after UCBT.

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Number of Participants With Platelet Engraftment	159 Participants

SECONDARY outcome

Timeframe: Day 42

Determine the incidence of neutrophil engraftment at day 42 after UCBT Patients diagnosed with graft failure (failure of absolute neutrophil count ANC > 5 x 10^8/L of donor origin by day +42)

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Number of Participants With Neutrophil Engraftment	21 Participants

SECONDARY outcome

Timeframe: Day 100

Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 after UCBT. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria following Przepiorka et al, 1995, Consensus Clinical Stage and Grade of Acute GVHD.

Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Number of Participants With Acute Graft-Versus-Host Disease Grade II-IV	106 Participants
Number of Participants With Acute Graft-Versus-Host Disease Grade III-IV	49 Participants

SECONDARY outcome

Timeframe: Year 1

Determine the incidence of chronic GVHD at 1 year after UCBT. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria.

Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Number of Participants With Chronic Graft-Versus-Host Disease	39 Participants

SECONDARY outcome

Timeframe: Day 21

Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Percentage Chimerism on Day 21	92.6 percentage of donor cells Standard Deviation 14.9

SECONDARY outcome

Timeframe: Day 100

Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Percentage Chimerism on Day 100	98.1 percentage of donor cells Standard Deviation 8.5

SECONDARY outcome

Timeframe: Month 6

Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Percentage Chimerism at 6 Months	98.1 percentage of donor cells Standard Deviation 11.3

SECONDARY outcome

Timeframe: 1 Year

Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Percentage Chimerism at 1 Year	99.1 percentage of donor cells Standard Deviation 8.5

SECONDARY outcome

Timeframe: 2 Years

Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.

Outcome measures

Measure	Unrelated UCBT for Blood Cancers n=212 Participants Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Percentage Chimerism at 2 Years	100 percentage of donor cells Standard Deviation 0.1

Adverse Events

Unrelated UCBT for Blood Cancers

Serious events: 92 serious events

Other events: 187 other events

Deaths: 161 deaths

Serious adverse events

Measure	Unrelated UCBT for Blood Cancers n=212 participants at risk Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome (ARDS)	1.9% 4/212 • Number of events 4 • Upto 2 years
Cardiac disorders cardiopulmonary arrest	0.47% 1/212 • Number of events 1 • Upto 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death	19.3% 41/212 • Number of events 41 • Upto 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Graft failure	4.2% 9/212 • Number of events 9 • Upto 2 years
Immune system disorders Graft versus host disease (GVHD)	6.1% 13/212 • Number of events 13 • Upto 2 years
Infections and infestations Infection	4.7% 10/212 • Number of events 11 • Upto 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progressive disease	0.47% 1/212 • Number of events 1 • Upto 2 years
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrage	0.47% 1/212 • Number of events 1 • Upto 2 years
Respiratory, thoracic and mediastinal disorders Pulmonary other	1.4% 3/212 • Number of events 3 • Upto 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) relapse	3.3% 7/212 • Number of events 7 • Upto 2 years
Blood and lymphatic system disorders Thrombocytopenia	0.47% 1/212 • Number of events 1 • Upto 2 years
Hepatobiliary disorders Veno-Occlusive Disease (VOD)	0.47% 1/212 • Number of events 1 • Upto 2 years

Other adverse events

Measure	Unrelated UCBT for Blood Cancers n=212 participants at risk Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
General disorders Multi organ failure	5.7% 12/212 • Number of events 13 • Upto 2 years
Blood and lymphatic system disorders Hemorrhage	5.7% 12/212 • Number of events 14 • Upto 2 years
Nervous system disorders Neurotoxicity	6.1% 13/212 • Number of events 14 • Upto 2 years
Nervous system disorders Neuropathy	7.5% 16/212 • Number of events 16 • Upto 2 years
Renal and urinary disorders Acute kidney injury	8.5% 18/212 • Number of events 18 • Upto 2 years
Gastrointestinal disorders GI bleeding	8.5% 18/212 • Number of events 19 • Upto 2 years
Vascular disorders Hypertension	29.2% 62/212 • Number of events 62 • Upto 2 years
Hepatobiliary disorders Veno-Occlusive Disease (VOD)	5.7% 12/212 • Number of events 19 • Upto 2 years
Metabolism and nutrition disorders Hyperglycemia	10.4% 22/212 • Number of events 22 • Upto 2 years
Renal and urinary disorders Dialysis	10.8% 23/212 • Number of events 23 • Upto 2 years
General disorders Engraftment syndrome	11.8% 25/212 • Number of events 25 • Upto 2 years
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome (ARDS)	12.3% 26/212 • Number of events 27 • Upto 2 years
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	16.0% 34/212 • Number of events 42 • Upto 2 years
Cardiac disorders Pericardial effusion	21.7% 46/212 • Number of events 52 • Upto 2 years
Respiratory, thoracic and mediastinal disorders Intubation	27.4% 58/212 • Number of events 74 • Upto 2 years
Respiratory, thoracic and mediastinal disorders Pneumonia	61.8% 131/212 • Number of events 297 • Upto 2 years
Infections and infestations Infection	59.4% 126/212 • Number of events 527 • Upto 2 years

Additional Information

Dr.Claudio G. Brunstein MD, PhD

Masonic Cancer Center, University of Minnesota

Phone: 612-625-3918

Email: bruns072@umn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place