Trial Outcomes & Findings for Randomized Double Cord Blood Transplant Study (NCT NCT00067002)

Last Updated: 2019-05-01

Results Overview

Engraftment is defined as a sustained ANC \> 0.5 x 10\^9/L for at least 3 consecutive days. Engraftment date is the first of the 3 days with sustained absolute neutrophil count (ANC) \>/= 0.5 x 10\^9/L.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

110 participants

Primary outcome timeframe

First 100 days, evaluation and blood tests twice weekly

Results posted on

2019-05-01

Participant Flow

Recruitment Period: April 10, 2003 to October 3, 2011. All recruitment done at The University of Texas MD Anderson Cancer Center.

Of the 110 participants registered, five were excluded prior to assignment to groups.

Participant milestones

Participant milestones
Measure	Double Cord Blood Transplant Group (Un-Manipulated) Transplantation of Two Unmanipulated Cord Blood (CB) units. Rituxan 375 mg/m2 by vein (IV) Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3. Expanded allogeneic cord blood (CB): Transplantation of Two Unmanipulated Cord Blood Units.	One Expanded Cord Blood Transplant Group (Expanded) One Unmanipulated and One Expanded Cord Blood Unit. Rituxan: 375 mg/m2 by vein on Day - 9 for patients with CD20 + malignancies. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.
Overall Study STARTED	52	53
Overall Study COMPLETED	45	44
Overall Study NOT COMPLETED	7	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Double Cord Blood Transplant Group (Un-Manipulated) Transplantation of Two Unmanipulated Cord Blood (CB) units. Rituxan 375 mg/m2 by vein (IV) Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3. Expanded allogeneic cord blood (CB): Transplantation of Two Unmanipulated Cord Blood Units.	One Expanded Cord Blood Transplant Group (Expanded) One Unmanipulated and One Expanded Cord Blood Unit. Rituxan: 375 mg/m2 by vein on Day - 9 for patients with CD20 + malignancies. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.
Overall Study Early Death	1	2
Overall Study Delayed	1	1
Overall Study Graft Failure	5	6

Baseline Characteristics

Randomized Double Cord Blood Transplant Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Un-Manipulated CB Arm n=52 Participants Transplantation of Two Unmanipulated CB units. Rituxan 375 mg/m2 IV Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3.	Expanded CB Arm n=53 Participants Transplantation One Unmanipulated and One Expanded CB Unit. Rituxan: 375 mg/m2 IV on Day - 9 for CD20 + malignancies. Fludarabine 40 mg/m2 IV on Days -6 to -3. Cyclophosphamide 50 mg/kg IV on Day -6. Mesna 10 mg/kg IV before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). TBI Day -1 at 2 Gy.	Total n=105 Participants Total of all reporting groups
Age, Continuous	42 years n=5 Participants	44 years n=7 Participants	43 years n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	12 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	41 Participants n=7 Participants	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	34 Participants n=5 Participants	33 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	42 Participants n=5 Participants	43 Participants n=7 Participants	85 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment United States	52 Participants n=5 Participants	53 Participants n=7 Participants	105 Participants n=5 Participants

PRIMARY outcome

Timeframe: First 100 days, evaluation and blood tests twice weekly

Outcome measures

Outcome measures
Measure	Un-Manipulated CB Arm n=52 Participants Transplantation of Two Unmanipulated CB units. Rituxan 375 mg/m2 IV Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3.	Expanded CB Arm n=53 Participants Transplantation One Unmanipulated and One Expanded CB Unit. Rituxan: 375 mg/m2 IV on Day - 9 for CD20 + malignancies. Fludarabine 40 mg/m2 IV on Days -6 to -3. Cyclophosphamide 50 mg/kg IV on Day -6. Mesna 10 mg/kg IV before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). TBI Day -1 at 2 Gy.
Time To Neutrophil Engraftment	17 Days Interval 5.0 to 45.0	15 Days Interval 4.0 to 43.0

PRIMARY outcome

Timeframe: First 100 days, evaluation and blood tests twice weekly

Engraftment defined as a sustained absolute neutrophil count (ANC) \> 0.5 x 10\^9/L for at least 3 consecutive days. Engraftment Failure defined as ANC \<500/ul by day +42 and participant has no evidence of donor chimerism on bone marrow examination.

Outcome measures

Outcome measures
Measure	Un-Manipulated CB Arm n=52 Participants Transplantation of Two Unmanipulated CB units. Rituxan 375 mg/m2 IV Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3.	Expanded CB Arm n=53 Participants Transplantation One Unmanipulated and One Expanded CB Unit. Rituxan: 375 mg/m2 IV on Day - 9 for CD20 + malignancies. Fludarabine 40 mg/m2 IV on Days -6 to -3. Cyclophosphamide 50 mg/kg IV on Day -6. Mesna 10 mg/kg IV before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). TBI Day -1 at 2 Gy.
Number of Participants With Engraftment	45 Participants	44 Participants

SECONDARY outcome

Timeframe: Review over first 100 days

Population: Acute GVHD percentage calculated using engrafted participants only (n=89; expanded 44; un-manipulated 45)

Number of participants who display features of acute GVHD within 100 days of transplant.

Outcome measures

Outcome measures
Measure	Un-Manipulated CB Arm n=45 Participants Transplantation of Two Unmanipulated CB units. Rituxan 375 mg/m2 IV Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3.	Expanded CB Arm n=44 Participants Transplantation One Unmanipulated and One Expanded CB Unit. Rituxan: 375 mg/m2 IV on Day - 9 for CD20 + malignancies. Fludarabine 40 mg/m2 IV on Days -6 to -3. Cyclophosphamide 50 mg/kg IV on Day -6. Mesna 10 mg/kg IV before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). TBI Day -1 at 2 Gy.
Rate of Acute Graft Versus Host Disease (GVHD)	29 Participants	24 Participants

SECONDARY outcome

Timeframe: Up to one year

Population: Chronic GVHD percentage calculated using engrafted patients and alive after 100 days (n=77; expanded 40; unmanipulated 37)

Number of participants who present GVHD post-transplant and display features of chronic GVHD. Diagnostic and distinctive features of chronic GVHD are present. There are no features of acute GVHD.

Outcome measures

Outcome measures
Measure	Un-Manipulated CB Arm n=37 Participants Transplantation of Two Unmanipulated CB units. Rituxan 375 mg/m2 IV Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3.	Expanded CB Arm n=40 Participants Transplantation One Unmanipulated and One Expanded CB Unit. Rituxan: 375 mg/m2 IV on Day - 9 for CD20 + malignancies. Fludarabine 40 mg/m2 IV on Days -6 to -3. Cyclophosphamide 50 mg/kg IV on Day -6. Mesna 10 mg/kg IV before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). TBI Day -1 at 2 Gy.
Rate of Chronic GVHD Overall Chronic GVHD	16 Participants	20 Participants
Rate of Chronic GVHD Limited	10 Participants	14 Participants
Rate of Chronic GVHD Extensive	9 Participants	13 Participants

SECONDARY outcome

Timeframe: Following first 100 days, up to one year

Population: For the Acute GVHD the analysis was performed on patients with GVHD in the first 100 days.

The severity of acute GVHD is determined by an assessment of the degree of involvement of the skin, liver, and gastrointestinal tract. The stages of individual organ involvement is assessed using Glucksberg grade (I-IV) where Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Outcome measures

Outcome measures
Measure	Un-Manipulated CB Arm n=45 Participants Transplantation of Two Unmanipulated CB units. Rituxan 375 mg/m2 IV Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3.	Expanded CB Arm n=44 Participants Transplantation One Unmanipulated and One Expanded CB Unit. Rituxan: 375 mg/m2 IV on Day - 9 for CD20 + malignancies. Fludarabine 40 mg/m2 IV on Days -6 to -3. Cyclophosphamide 50 mg/kg IV on Day -6. Mesna 10 mg/kg IV before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). TBI Day -1 at 2 Gy.
Number of Participants Severity of Acute GVHD by Treatment Arm Grade ≥ 3	6 Participants	2 Participants
Number of Participants Severity of Acute GVHD by Treatment Arm Grade ≤ 2	20 Participants	15 Participants
Number of Participants Severity of Acute GVHD by Treatment Arm No GVHD	19 Participants	27 Participants

Adverse Events

Un-Manipulated CB Arm

Serious events: 9 serious events

Other events: 52 other events

Deaths: 0 deaths

Expanded CB Arm

Serious events: 4 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Simrit Parmar, MD/Associate Professor, Stem Cell Transplantation

UT MD Anderson Cancer Center

Phone: 713-792-7734

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Un-Manipulated CB Arm n=52 participants at risk Transplantation of Two Unmanipulated CB units. Rituxan 375 mg/m2 IV Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3.	Expanded CB Arm n=53 participants at risk Transplantation One Unmanipulated and One Expanded CB Unit. Rituxan: 375 mg/m2 IV on Day - 9 for CD20 + malignancies. Fludarabine 40 mg/m2 IV on Days -6 to -3. Cyclophosphamide 50 mg/kg IV on Day -6. Mesna 10 mg/kg IV before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). TBI Day -1 at 2 Gy.
Blood and lymphatic system disorders Multi-Organ Failure	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome (ARDS)	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Investigations Bilirubin Increase	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Metabolism and nutrition disorders Elevevated aspartate aminotransferase (SGOT)	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Respiratory, thoracic and mediastinal disorders Hemorrhage, Pulmonary	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Hepatobiliary disorders Hepatic Changes (Other: Unknown)	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Infections and infestations Infection	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Renal and urinary disorders Renal Failure	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Investigations Alanine aminotransferase increased	1.9% 1/52 • Number of events 1 • Adverse event collection through first 100 days following transplant.	0.00% 0/53 • Adverse event collection through first 100 days following transplant.
Nervous system disorders Altered Mental State	0.00% 0/52 • Adverse event collection through first 100 days following transplant.	1.9% 1/53 • Number of events 1 • Adverse event collection through first 100 days following transplant.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/52 • Adverse event collection through first 100 days following transplant.	1.9% 1/53 • Number of events 1 • Adverse event collection through first 100 days following transplant.
Infections and infestations Infection without Neutropenia	0.00% 0/52 • Adverse event collection through first 100 days following transplant.	1.9% 1/53 • Number of events 1 • Adverse event collection through first 100 days following transplant.
Blood and lymphatic system disorders Neutrophils (Absolute Neutrophil Count (ANC)) Decreased	0.00% 0/52 • Adverse event collection through first 100 days following transplant.	1.9% 1/53 • Number of events 1 • Adverse event collection through first 100 days following transplant.