Trial Outcomes & Findings for IPA Targeted Adoptive Immunotherapy vs Adult Haplo-identical Cell Infusion During Induction of High Risk Leukemia (NCT NCT02508324)
NCT ID: NCT02508324
Last Updated: 2024-02-13
Results Overview
Evaluate the safety of adoptive immunotherapy with Non-Inherited Maternal Antigen (NIMA) compatible, Inherited Paternal Antigen (IPA) targeted CBU or with haplo-identical stem cells after conventional induction therapy for very high risk AML or MDS. Assessed by development of cytokine release syndrome (CRS) or graft-versus-host disease (GVHD) after adoptive immunotherapy.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
43 participants
Primary outcome timeframe
6 months
Results posted on
2024-02-13
Participant Flow
Participant milestones
| Measure |
Cord Blood Unit
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
|---|---|---|
|
Overall Study
STARTED
|
43
|
0
|
|
Overall Study
COMPLETED
|
43
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
IPA Targeted Adoptive Immunotherapy vs Adult Haplo-identical Cell Infusion During Induction of High Risk Leukemia
Baseline characteristics by cohort
| Measure |
Cord Blood Unit
n=43 Participants
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
Total
n=43 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
|
35 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
8 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
32 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 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
|
10 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
10 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
|
7 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
22 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
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
43 participants
n=5 Participants
|
—
|
43 participants
n=5 Participants
|
|
Primary Malignancy
Acute Myeloid Leukemia
|
39 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Primary Malignancy
Myelodysplastic Syndrome
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Primary Malignancy
Chronic Myelogenous Leukemia
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
Evaluate the safety of adoptive immunotherapy with Non-Inherited Maternal Antigen (NIMA) compatible, Inherited Paternal Antigen (IPA) targeted CBU or with haplo-identical stem cells after conventional induction therapy for very high risk AML or MDS. Assessed by development of cytokine release syndrome (CRS) or graft-versus-host disease (GVHD) after adoptive immunotherapy.
Outcome measures
| Measure |
Cord Blood Unit
n=43 Participants
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
|---|---|---|
|
Safety of Cellular Immunotherapy as Measured by the Number of Participants Who Developed of Cytokine Release Syndrome (CRS) or Graft-versus-host Disease (GVHD) After Adoptive Immunotherapy
|
8 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
To assess the incidence and severity of Graft Versus Host Disease (GVHD), after conventional induction therapy followed by adoptive immunotherapy with NIMA compatible, IPA targeted CBU.
Outcome measures
| Measure |
Cord Blood Unit
n=43 Participants
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
|---|---|---|
|
Number of Participants Who Developed GVHD by Severity
Grade 1 GVHD
|
3 Participants
|
0 Participants
|
|
Number of Participants Who Developed GVHD by Severity
Grade 2 GVHD
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Developed GVHD by Severity
Grade 3 GVHD
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Developed GVHD by Severity
Grade 4 GVHD
|
2 Participants
|
0 Participants
|
|
Number of Participants Who Developed GVHD by Severity
No GVHD
|
38 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
Outcome measures
| Measure |
Cord Blood Unit
n=43 Participants
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
|---|---|---|
|
Number of Participants With Detectable Cord Blood or Haploidentical Chimerism After Adoptive Immunotherapy
|
16 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
Count of participants with who developed HLA-antibodies that precluded them from moving forward to transplant
Outcome measures
| Measure |
Cord Blood Unit
n=43 Participants
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
|---|---|---|
|
Number of Participants With HLA-antibodies That Precluded Them From Moving Forward to Transplant
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
To assess response rates after adoptive immunotherapy. Response to treatment is defined as effective cytoreduction (ie, \<5% residual blasts in a hypocellular bone marrow \[BM\] or no blasts in an acellular bone marrow \[aplasia\] obtained ∼14 days after infusion of the CB cells)
Outcome measures
| Measure |
Cord Blood Unit
n=43 Participants
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
|---|---|---|
|
Number of Participants Who Responded to Treatment
|
18 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
Number of participants that underwent a transplant after response to adoptive immunotherapy. Response to treatment is defined as effective cytoreduction (ie, \<5% residual blasts in a hypocellular bone marrow \[BM\] or no blasts in an acellular bone marrow \[aplasia\] obtained ∼14 days after infusion of the CB cells)
Outcome measures
| Measure |
Cord Blood Unit
n=13 Participants
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
|---|---|---|
|
Number of Participants That Underwent a Transplant After Response to Adoptive Immunotherapy
|
12 Participants
|
0 Participants
|
Adverse Events
Cord Blood Unit
Serious events: 15 serious events
Other events: 32 other events
Deaths: 5 deaths
Haploidentical
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cord Blood Unit
n=43 participants at risk
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Investigations
Acute Graft-versus-Host Disease
|
7.0%
3/43 • Number of events 3 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Adenovirus Infection
|
4.7%
2/43 • Number of events 2 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Cardiac disorders
Atrial Fibrillation
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Clostridium difficile infection
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Hepatobiliary disorders
Cholecystitis
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Gastrointestinal disorders
Diverticulitis
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Fungal Pneumonia
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Fungal sinusitis
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Vascular disorders
Hypotension
|
4.7%
2/43 • Number of events 2 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Hepatobiliary disorders
Hepatic Failure
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Investigations
Multiorgan Failure
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Pneumonia
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Vascular disorders
Presacral Hematoma
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Investigations
Post-Transplant Lymphoproliferative Disorder
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Sepsis
|
9.3%
4/43 • Number of events 4 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Vascular disorders
Thromboembolic event
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Injury, poisoning and procedural complications
Vascular Access Complication
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
Other adverse events
| Measure |
Cord Blood Unit
n=43 participants at risk
The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
CBU grafts in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x 10\^7 nucleated blood cells/kg.
umbilical cord blood unit (CBU): Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA.
|
Haploidentical
Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.).
Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.
haplo-identical cells (donor): Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.
|
|---|---|---|
|
Gastrointestinal disorders
Anal Fistula
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Metabolism and nutrition disorders
Anorexia
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Bacteremia
|
41.9%
18/43 • Number of events 19 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
BK Viruria
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Enterocolitis Infectious
|
16.3%
7/43 • Number of events 7 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
14.0%
6/43 • Number of events 6 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Fungal Pneumonia
|
4.7%
2/43 • Number of events 2 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Fungemia
|
4.7%
2/43 • Number of events 2 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Herpes simplex reactivation
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Pneumonia
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Sinusitis
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Skin Cellulitis
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Vascular disorders
Thromboembolic Event
|
2.3%
1/43 • Number of events 1 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Upper Respiratory Infection
|
18.6%
8/43 • Number of events 9 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
|
Infections and infestations
Urinary Tract Infection
|
9.3%
4/43 • Number of events 4 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
—
0/0 • 6 months
No subjects were enrolled onto the Haploidentical arm due to graft selection criteria and suitable cord blood units being identified for subjects.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place