Trial Outcomes & Findings for Donor Umbilical Cord Blood Transplant After Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Cancer (NCT NCT00963872)

NCT ID: NCT00963872

Last Updated: 2017-12-28

Results Overview

Efficacy of the pre-incubation of one of two umbilical cord blood (UCB) units with C3a as part of a unrelated donor double UCB nonmyeloablative transplantation in patients with high-risk hematological malignancies.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Day 180

Results posted on

2017-12-28

Participant Flow

Subjects were recruited at the time of clinic visit or hospitalization. Patients that were considered for umbilical cord transplant were approached with the study.

Subjects that were eligible for umbilical cord transplant were considered for the study.

Participant milestones

Participant milestones
Measure
Complement Fragment 3A - Small Cell Dose
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Overall Study
STARTED
25
6
Overall Study
COMPLETED
24
5
Overall Study
NOT COMPLETED
1
1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Donor Umbilical Cord Blood Transplant After Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Complement Fragment 3A - Small Cell Dose
n=25 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=6 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Total
n=31 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
19 Participants
n=5 Participants
5 Participants
n=7 Participants
24 Participants
n=5 Participants
Age, Categorical
>=65 years
6 Participants
n=5 Participants
1 Participants
n=7 Participants
7 Participants
n=5 Participants
Age, Continuous
55 years
STANDARD_DEVIATION 13.0 • n=5 Participants
50 years
STANDARD_DEVIATION 15.7 • n=7 Participants
54 years
STANDARD_DEVIATION 13.4 • n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
2 Participants
n=7 Participants
11 Participants
n=5 Participants
Sex: Female, Male
Male
16 Participants
n=5 Participants
4 Participants
n=7 Participants
20 Participants
n=5 Participants
Region of Enrollment
United States
25 participants
n=5 Participants
6 participants
n=7 Participants
31 participants
n=5 Participants

PRIMARY outcome

Timeframe: Day 180

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Efficacy of the pre-incubation of one of two umbilical cord blood (UCB) units with C3a as part of a unrelated donor double UCB nonmyeloablative transplantation in patients with high-risk hematological malignancies.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Number of Patients With the Complement 3a (C3a) Unit Predominating
9 participants
5 participants

SECONDARY outcome

Timeframe: Day 42

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Achieving 500 neutrophils/uL by day 42.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Neutrophil Engraftment
22 participants
5 participants

SECONDARY outcome

Timeframe: Day 28

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Percentage of donor DNA present in the peripheral blood

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Donor Chimerism in Blood
92 percentage of donor DNA
Standard Deviation 15
96 percentage of donor DNA
Standard Deviation 8

SECONDARY outcome

Timeframe: Day 0 through Day 100

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Development of graft-versus-host disease through day 100.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Incidence of Grades II-IV Graft-vs-host Disease
8 participants
1 participants

SECONDARY outcome

Timeframe: Day 180

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Deaths not due to relapse.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Non-Relapse Mortality
3 participants
0 participants

SECONDARY outcome

Timeframe: Day 360

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Survival (alive) from transplantation to last follow-up.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Overall Survival
14 participants
5 participants

SECONDARY outcome

Timeframe: Day 21

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Percentage of donor DNA in the bone marrow.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Bone Marrow Chimerism
84 percentage of donor DNA
Standard Deviation 25
89 percentage of donor DNA
Standard Deviation 23

SECONDARY outcome

Timeframe: Day 360

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Patients who developed chronic graft-versus-host disease.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Chronic Graft-Versus-Host Disease
0 participants
0 participants

SECONDARY outcome

Timeframe: Day 360

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Patients who developed disease relapse after transplantation.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Relapse of Disease
10 participants
0 participants

SECONDARY outcome

Timeframe: Day 360

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Patients who developed disease progression after transplantation.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Disease Progression
0 participants
0 participants

SECONDARY outcome

Timeframe: Day 180

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Number of patients with \>20,000 platelets/uL by day 180

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Platelet Recovery
19 participants
5 participants

SECONDARY outcome

Timeframe: Day 60

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Percentage of donor DNA present in the peripheral blood

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Donor Chimerism in Blood
91 percentage of donor DNA
Standard Deviation 23
97 percentage of donor DNA
Standard Deviation 4

SECONDARY outcome

Timeframe: 0 to 100 days

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Development of graft-versus-host disease by day 100.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Incidence of Grades III-IV Graft-vs-host Disease
2 participants
0 participants

SECONDARY outcome

Timeframe: Day 360

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Deaths not due to relapse.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Non-relapse Mortality
3 participants
0 participants

SECONDARY outcome

Timeframe: 720 days

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Survival (alive) from transplantation to last follow-up at day 720.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Overall Survival at Day 720
13 participants
5 participants

SECONDARY outcome

Timeframe: Day 720

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Patients who developed disease relapse after transplantation.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Relapse of Disease
11 participants
1 participants

SECONDARY outcome

Timeframe: Day 720

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Patients who developed disease progression after transplantation.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Disease Progression
0 participants
0 participants

SECONDARY outcome

Timeframe: Day 100

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Percentage of donor DNA in the bone marrow.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Donor Chimerism
90 percentage of donor DNA
Standard Deviation 22
94 percentage of donor DNA
Standard Deviation 19

SECONDARY outcome

Timeframe: Day 180

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Percentage of donor DNA in the bone marrow.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Donor Chimerism
99 percentage of donor DNA
Standard Deviation 3
100 percentage of donor DNA
Standard Deviation 0

SECONDARY outcome

Timeframe: Day 360

Population: Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.

Percentage of donor DNA in the bone marrow.

Outcome measures

Outcome measures
Measure
Complement Fragment 3A - Small Cell Dose
n=24 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 Participants
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Donor Chimerism
93 percentage of donor DNA
Standard Deviation 19
100 percentage of donor DNA
Standard Deviation 0

Adverse Events

Complement Fragment 3A - Small Cell Dose

Serious events: 21 serious events
Other events: 24 other events
Deaths: 0 deaths

Complement Fragment A - Larger Cell Dose

Serious events: 5 serious events
Other events: 5 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Complement Fragment 3A - Small Cell Dose
n=24 participants at risk
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 participants at risk
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Blood and lymphatic system disorders
Blood and lymphatic disorders- Other
41.7%
10/24 • Number of events 10 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Blood and lymphatic system disorders
Leukocytosis
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Gastrointestinal disorders
Diarrhea
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Gastrointestinal disorders
Nausea
4.2%
1/24 • Number of events 2 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Gastrointestinal disorders
Pancreatitis
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Gastrointestinal disorders
Stomach pain
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Gastrointestinal disorders
Vomiting
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
General disorders
Death NOS
8.3%
2/24 • Number of events 2 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
General disorders
Fever
20.8%
5/24 • Number of events 5 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
General disorders
Infusion related reaction
0.00%
0/24 • 100 days after umbilical cord blood transplant
20.0%
1/5 • Number of events 1 • 100 days after umbilical cord blood transplant
Infections and infestations
Catheter related infection
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Infections and infestations
Lung infection
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
20.0%
1/5 • Number of events 1 • 100 days after umbilical cord blood transplant
Investigations
Aspartate aminotransferase increased
0.00%
0/24 • 100 days after umbilical cord blood transplant
20.0%
1/5 • Number of events 1 • 100 days after umbilical cord blood transplant
Nervous system disorders
Peripheral sensory neuropathy
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Nervous system disorders
Seizure
8.3%
2/24 • Number of events 2 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Psychiatric disorders
Confusion
8.3%
2/24 • Number of events 2 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Renal and urinary disorders
Hematuria
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Renal and urinary disorders
Renal and urinary disorders- Other
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
40.0%
2/5 • Number of events 2 • 100 days after umbilical cord blood transplant
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Respiratory, thoracic and mediastinal disorders
Dyspnea
0.00%
0/24 • 100 days after umbilical cord blood transplant
20.0%
1/5 • Number of events 1 • 100 days after umbilical cord blood transplant
Respiratory, thoracic and mediastinal disorders
Pleuritic plan
4.2%
1/24 • Number of events 1 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Vascular disorders
Thromboembolic event
0.00%
0/24 • 100 days after umbilical cord blood transplant
20.0%
1/5 • Number of events 1 • 100 days after umbilical cord blood transplant

Other adverse events

Other adverse events
Measure
Complement Fragment 3A - Small Cell Dose
n=24 participants at risk
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
Complement Fragment A - Larger Cell Dose
n=5 participants at risk
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
Skin and subcutaneous tissue disorders
Rash
12.5%
3/24 • Number of events 3 • 100 days after umbilical cord blood transplant
0.00%
0/5 • 100 days after umbilical cord blood transplant
Blood and lymphatic system disorders
Hypertension
100.0%
24/24 • Number of events 24 • 100 days after umbilical cord blood transplant
80.0%
4/5 • Number of events 4 • 100 days after umbilical cord blood transplant
Cardiac disorders
Sinus tachycardia
8.3%
2/24 • Number of events 2 • 100 days after umbilical cord blood transplant
20.0%
1/5 • Number of events 1 • 100 days after umbilical cord blood transplant
Nervous system disorders
Neurologic disorder
16.7%
4/24 • Number of events 4 • 100 days after umbilical cord blood transplant
20.0%
1/5 • Number of events 1 • 100 days after umbilical cord blood transplant
Cardiac disorders
Sinus bradycardia
29.2%
7/24 • Number of events 7 • 100 days after umbilical cord blood transplant
40.0%
2/5 • Number of events 2 • 100 days after umbilical cord blood transplant

Additional Information

Dr. Claudio Brunstein

University of Minnesota

Phone: 612-625-3918

Results disclosure agreements

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