Trial Outcomes & Findings for Methods to Enhance the Safety and Effectiveness of Stem Cell Transplants (NCT NCT00378534)
NCT ID: NCT00378534
Last Updated: 2021-06-16
Results Overview
Subjects with hematological malignancies receiving a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90. The subjects receiving allogeneic stem cell transplantation will have stem cell product prepared using Miltenyi CliniMacs system to determine the overall survival and non-relapse mortality at day +200.
COMPLETED
PHASE2
116 participants
Day 200
2021-06-16
Participant Flow
Participant milestones
| Measure |
T Cell Depletion Transplant Participants
Participants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90.
|
Stem Cell Donors
An HLA 6/6 identical family member will be co-enrolled into this study as a stem cell donor. The stem cell collection aspect of this protocol is not investigational.
|
|---|---|---|
|
Overall Study
STARTED
|
58
|
58
|
|
Overall Study
COMPLETED
|
55
|
58
|
|
Overall Study
NOT COMPLETED
|
3
|
0
|
Reasons for withdrawal
| Measure |
T Cell Depletion Transplant Participants
Participants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90.
|
Stem Cell Donors
An HLA 6/6 identical family member will be co-enrolled into this study as a stem cell donor. The stem cell collection aspect of this protocol is not investigational.
|
|---|---|---|
|
Overall Study
Participants did not receive transplant
|
3
|
0
|
Baseline Characteristics
Methods to Enhance the Safety and Effectiveness of Stem Cell Transplants
Baseline characteristics by cohort
| Measure |
T Cell Depletion Transplant Participants
n=58 Participants
Participants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90
|
Stem Cell Donors
n=58 Participants
An HLA 6/6 identical family member will be co-enrolled into this study as a stem cell donor. The stem cell collection aspect of this protocol is not investigational.
|
Total
n=116 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
52 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
103 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
30 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
27 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 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
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 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
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
28 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
58 participants
n=5 Participants
|
58 participants
n=7 Participants
|
116 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 200Subjects with hematological malignancies receiving a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90. The subjects receiving allogeneic stem cell transplantation will have stem cell product prepared using Miltenyi CliniMacs system to determine the overall survival and non-relapse mortality at day +200.
Outcome measures
| Measure |
T Cell Depletion Transplant Participants
n=55 Participants
Participants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90.
|
|---|---|
|
Survival and Non-relapse Mortality at Day +200 Using the Miltenyi Reagent System
Survival at day 200
|
43 participants
|
|
Survival and Non-relapse Mortality at Day +200 Using the Miltenyi Reagent System
Non-relapse mortality
|
4 participants
|
SECONDARY outcome
Timeframe: Day 200Number of participants with relapse of disease by day 200
Outcome measures
| Measure |
T Cell Depletion Transplant Participants
n=55 Participants
Participants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90.
|
|---|---|
|
Number of Participants With Relapse of Disease
|
17 Participants
|
SECONDARY outcome
Timeframe: 100 daysNumber of participants who developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as defined by CIMBTR criteria for Organ Stages of Acute GVHD. Grades are defined as: Grade I: Skin = Maculopapular rash\< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day. Grade II: Skin = rash on 25-50 percent body surface area; Liver = Total Bilirubin 3.1-6.0 mg/dL; Lower GI = Diarrhea 1001-1500 mL/day. Grade III: Skin = Rash on \>50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea \> 1500 mL/day. Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin \>15 mg/dL; Lower GI = Severe abdominal pain with or without ileus. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Outcome measures
| Measure |
T Cell Depletion Transplant Participants
n=55 Participants
Participants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90.
|
|---|---|
|
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV
Acute GVHD, Grade I
|
14 Participants
|
|
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV
Acute GVHD, Grade II
|
16 Participants
|
|
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV
Acute GVHD, Grade III
|
9 Participants
|
|
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV
Acute GVHD, Grade IV
|
1 Participants
|
SECONDARY outcome
Timeframe: 36 monthsNumber of incidences of participants who developed Limited Chronic Graft vs Host Disease (GVHD). Limited disease is characterized by localized skin involvement and/or evidence of hepatic dysfunction. Limited disease is associated with a favorable outcome without systemic therapy, while extensive disease patients have an unfavorable outcome.
Outcome measures
| Measure |
T Cell Depletion Transplant Participants
n=55 Participants
Participants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90.
|
|---|---|
|
Number of Participants Who Developed Limited Chronic GVHD
|
8 Participants
|
SECONDARY outcome
Timeframe: 36 monthsNumber of participants with extensive, Chronic Graft vs Host Disease (GVHD). Extensive chronic GVHD is defined as GVHD occurring after day 100 that did not meet the definition of limited chronic GVHD. Extensive disease presents either with generalized skin involvement, or with localized skin involvement or hepatic dysfunction plus at least one of the following: * Liver histology showing chronic progressive hepatitis, bridging necrosis, or cirrhosis * Involvement of the eye (Schirmer's test with less than 5 mm wetting) (see "Diagnosis and classification of Sjögren's syndrome") * Involvement of minor salivary glands or oral mucosa (as demonstrated on labial or mucosal biopsy specimen) * Involvement of any other target organ
Outcome measures
| Measure |
T Cell Depletion Transplant Participants
n=55 Participants
Participants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90.
|
|---|---|
|
Number of Participants Who Develop Extensive GVHD
|
18 Participants
|
Adverse Events
T Cell Depletion Transplant Participants
Stem Cell Donors
Serious adverse events
| Measure |
T Cell Depletion Transplant Participants
n=58 participants at risk
Participants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90.
|
Stem Cell Donors
n=58 participants at risk
An HLA 6/6 identical family member will be co-enrolled into this study as a stem cell donor. The stem cell collection aspect of this protocol is not investigational.
|
|---|---|---|
|
Blood and lymphatic system disorders
Graft failure
|
5.2%
3/58 • Number of events 3 • 36 months
|
0.00%
0/58 • 36 months
|
|
Infections and infestations
Infection
|
12.1%
7/58 • Number of events 7 • 36 months
|
0.00%
0/58 • 36 months
|
|
Immune system disorders
GVHD
|
6.9%
4/58 • Number of events 4 • 36 months
|
0.00%
0/58 • 36 months
|
|
Immune system disorders
Posterior reversible encephalopathy syndrome
|
1.7%
1/58 • Number of events 1 • 36 months
|
0.00%
0/58 • 36 months
|
|
Musculoskeletal and connective tissue disorders
Hip fracture
|
1.7%
1/58 • Number of events 1 • 36 months
|
0.00%
0/58 • 36 months
|
|
Vascular disorders
Deep vein thrombosis
|
1.7%
1/58 • Number of events 1 • 36 months
|
0.00%
0/58 • 36 months
|
|
Cardiac disorders
Arrythmia
|
1.7%
1/58 • Number of events 1 • 36 months
|
0.00%
0/58 • 36 months
|
|
Blood and lymphatic system disorders
Hemorrhage
|
1.7%
1/58 • Number of events 1 • 36 months
|
0.00%
0/58 • 36 months
|
|
Blood and lymphatic system disorders
Microangiopathy Anemia
|
1.7%
1/58 • Number of events 1 • 36 months
|
0.00%
0/58 • 36 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary emboli
|
1.7%
1/58 • Number of events 1 • 36 months
|
0.00%
0/58 • 36 months
|
Other adverse events
Adverse event data not reported
Additional Information
Sara Hauffe, RN Protocol Liaison
NIH NHLBI OCD DIR ORIC
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place