Trial Outcomes & Findings for Reduced Intensity Conditioning for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (BMT CTN 1204) (NCT NCT01998633)
NCT ID: NCT01998633
Last Updated: 2022-12-08
Results Overview
Overall survival is defined as survival of death from any cause.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
47 participants
Primary outcome timeframe
1 year and 18 months post-transplant
Results posted on
2022-12-08
Participant Flow
Participant milestones
| Measure |
Hematopoietic Stem Cell Transplant
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
|---|---|
|
Overall Study
STARTED
|
47
|
|
Overall Study
COMPLETED
|
46
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Hematopoietic Stem Cell Transplant
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
|---|---|
|
Overall Study
Death
|
1
|
Baseline Characteristics
Participants with Primary Immune Deficiencies
Baseline characteristics by cohort
| Measure |
Hemophagocytic Lymphohistiocytosis (HLH)
n=34 Participants
Participants with Hemophagocytic Lymphohistiocytosis
|
Other Primary Immune Deficiencies (PID)
n=12 Participants
Participants with other primary immune deficiencies, including chronic active EBV disease, chronic granulomatous disease, hyper-immunoglobulin M syndrome, and immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
0-9 Years
|
26 Participants
n=34 Participants
|
8 Participants
n=12 Participants
|
34 Participants
n=46 Participants
|
|
Age, Customized
10-19 Years
|
7 Participants
n=34 Participants
|
2 Participants
n=12 Participants
|
9 Participants
n=46 Participants
|
|
Age, Customized
20-29 Years
|
1 Participants
n=34 Participants
|
2 Participants
n=12 Participants
|
3 Participants
n=46 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=34 Participants
|
4 Participants
n=12 Participants
|
15 Participants
n=46 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=34 Participants
|
8 Participants
n=12 Participants
|
31 Participants
n=46 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=34 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=46 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=34 Participants
|
0 Participants
n=12 Participants
|
2 Participants
n=46 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=34 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=46 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=34 Participants
|
2 Participants
n=12 Participants
|
6 Participants
n=46 Participants
|
|
Race (NIH/OMB)
White
|
26 Participants
n=34 Participants
|
9 Participants
n=12 Participants
|
35 Participants
n=46 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=34 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=46 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=34 Participants
|
1 Participants
n=12 Participants
|
3 Participants
n=46 Participants
|
|
Karnofsky Performance Score (KPS)
90-100
|
24 Participants
n=34 Participants
|
10 Participants
n=12 Participants
|
34 Participants
n=46 Participants
|
|
Karnofsky Performance Score (KPS)
80
|
6 Participants
n=34 Participants
|
2 Participants
n=12 Participants
|
8 Participants
n=46 Participants
|
|
Karnofsky Performance Score (KPS)
70
|
2 Participants
n=34 Participants
|
0 Participants
n=12 Participants
|
2 Participants
n=46 Participants
|
|
Karnofsky Performance Score (KPS)
60
|
1 Participants
n=34 Participants
|
0 Participants
n=12 Participants
|
1 Participants
n=46 Participants
|
|
Karnofsky Performance Score (KPS)
50
|
1 Participants
n=34 Participants
|
0 Participants
n=12 Participants
|
1 Participants
n=46 Participants
|
|
Primary Immune Deficiency Type
Chronic Active Epstein-Barr Virus
|
—
|
3 Participants
n=12 Participants • Participants with Primary Immune Deficiencies
|
3 Participants
n=12 Participants • Participants with Primary Immune Deficiencies
|
|
Primary Immune Deficiency Type
Chronic Granulomatous Disease
|
—
|
5 Participants
n=12 Participants • Participants with Primary Immune Deficiencies
|
5 Participants
n=12 Participants • Participants with Primary Immune Deficiencies
|
|
Primary Immune Deficiency Type
Hyperimmunoglobulin M Syndrome
|
—
|
2 Participants
n=12 Participants • Participants with Primary Immune Deficiencies
|
2 Participants
n=12 Participants • Participants with Primary Immune Deficiencies
|
|
Primary Immune Deficiency Type
IPEX
|
—
|
2 Participants
n=12 Participants • Participants with Primary Immune Deficiencies
|
2 Participants
n=12 Participants • Participants with Primary Immune Deficiencies
|
|
Donor Type
HLA Matched Sibling
|
7 Participants
n=34 Participants
|
0 Participants
n=12 Participants
|
7 Participants
n=46 Participants
|
|
Donor Type
1 HLA Locus Mismatched Relative
|
0 Participants
n=34 Participants
|
1 Participants
n=12 Participants
|
1 Participants
n=46 Participants
|
|
Donor Type
HLA Matched Unrelated
|
16 Participants
n=34 Participants
|
9 Participants
n=12 Participants
|
25 Participants
n=46 Participants
|
|
Donor Type
1 HLA Locus Mismatched Unrelated
|
11 Participants
n=34 Participants
|
2 Participants
n=12 Participants
|
13 Participants
n=46 Participants
|
PRIMARY outcome
Timeframe: 1 year and 18 months post-transplantOverall survival is defined as survival of death from any cause.
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=46 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
|
|---|---|---|
|
Percentage of Participants With Overall Survival (OS)
1 year OS
|
80.4 percentage of participants
Interval 68.6 to 88.2
|
—
|
|
Percentage of Participants With Overall Survival (OS)
18 month OS
|
66.7 percentage of participants
Interval 52.9 to 77.3
|
—
|
SECONDARY outcome
Timeframe: 1 year and 18 months post-transplantOverall survival is defined as survival of death from any cause.
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=34 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
n=12 Participants
|
|---|---|---|
|
Percentage of Participants With Overall Survival (OS) by Disease Type
1 year OS
|
82.4 percentage of participants
Interval 68.4 to 90.6
|
75.0 percentage of participants
Interval 47.4 to 89.5
|
|
Percentage of Participants With Overall Survival (OS) by Disease Type
18 month OS
|
68.0 percentage of participants
Interval 51.8 to 79.7
|
62.5 percentage of participants
Interval 32.7 to 82.0
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Participants with HLH
Systemic HLH Reactivation: Post-transplant HLH reactivation is defined by clinical and lab evidence of pathologic inflammation (persistent fever, progressive cytopenias, rising ferritin and soluble IL2Rα, decreasing fibrinogen, hepatosplenomegaly, end-organ damage) not attributable to other causes. Central nervous system (CNS) HLH Reactivation: Reactivation of CNS inflammation in patients with HLH may present with or without altered mental status and is defined by pleocytosis in Cerebrospinal fluid (CSF) or an MRI consistent with CNS inflammation not attributable to other causes.
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=34 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
|
|---|---|---|
|
Percentage of HLH Participants With HLH Reactivation Post-Transplant
|
14.7 percentage of participants
Interval 5.2 to 28.7
|
—
|
SECONDARY outcome
Timeframe: Day 42 post-transplantTime to absolute neutrophil count (ANC) engraftment is defined as the first of three measurements on different days that the patient has an absolute neutrophil count of ≥ 500x10\^6/liter following conditioning regimen induced nadir.
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=46 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
|
|---|---|---|
|
Percentage of Participants With Neutrophil Engraftment
|
100.0 percentage of participants
Interval 90.8 to 100.0
|
—
|
SECONDARY outcome
Timeframe: Day 100 post-transplantPlatelet engraftment is defined as the first day of a minimum of three measurements on different days that the patient has achieved a platelet count \> 20,000 / microliter AND the patient is platelet transfusion independent for a minimum of seven days following conditioning regimen induced nadir.
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=46 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
|
|---|---|---|
|
Percentage of Participants With Platelet Engraftment
|
88.9 percentage of participants
Interval 73.3 to 95.6
|
—
|
SECONDARY outcome
Timeframe: 1 year post-transplantSustained engraftment is defined as the occurrence of whole blood donor chimerism \> 5% by Day 42 accompanied by the absence of any primary or secondary graft failure. Primary graft failure is defined as \< 5% donor chimerism by Day +42, second stem cell infusion, DLI (except in the case of donor CTLs given for infection control), or second HCT following original HCT. Secondary graft failure is defined as \< 5% donor chimerism following initial engraftment.
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=46 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
|
|---|---|---|
|
Percentage of Participants Alive With Sustained Engraftment
|
39.1 percentage of participants
Interval 25.1 to 54.6
|
—
|
SECONDARY outcome
Timeframe: 1 year post-transplantSustained engraftment is defined as the occurrence of whole blood donor chimerism \> 5% by Day 42 accompanied by the absence of any primary or secondary graft failure. Primary graft failure is defined as \< 5% donor chimerism by Day +42, second stem cell infusion, DLI (except in the case of donor CTLs given for infection control), or second HCT following original HCT. Secondary graft failure is defined as \< 5% donor chimerism following initial engraftment.
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=34 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
n=12 Participants
|
|---|---|---|
|
Percentage of Participants Alive With Sustained Engraftment by Disease Type
|
41.2 percentage of participants
Interval 24.7 to 59.3
|
33.3 percentage of participants
Interval 9.9 to 65.1
|
SECONDARY outcome
Timeframe: 1 year post-transplantAcute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1. 2-3 mg/dL 2. 3.01-6 mg/dL 3. 6.01-15.0 mg/dL 4. \>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=46 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
|
|---|---|---|
|
Number of Participants With Acute Graft-Versus-Host Disease (GVHD)
Grade 0 or I
|
35 Participants
|
—
|
|
Number of Participants With Acute Graft-Versus-Host Disease (GVHD)
Grade II
|
3 Participants
|
—
|
|
Number of Participants With Acute Graft-Versus-Host Disease (GVHD)
Grade III
|
5 Participants
|
—
|
|
Number of Participants With Acute Graft-Versus-Host Disease (GVHD)
Grade IV
|
3 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 100 and 6 months post-transplantAcute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1. 2-3 mg/dL 2. 3.01-6 mg/dL 3. 6.01-15.0 mg/dL 4. \>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=46 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
|
|---|---|---|
|
Percentage of Participants With Grade II-IV and Grade III-IV Acute GVHD
Grade II-IV Acute GVHD at Day 100
|
17.4 percentage of participants
Interval 8.1 to 29.7
|
—
|
|
Percentage of Participants With Grade II-IV and Grade III-IV Acute GVHD
Grade II-IV Acute GVHD at 6 Months
|
26.1 percentage of participants
Interval 14.4 to 39.4
|
—
|
|
Percentage of Participants With Grade II-IV and Grade III-IV Acute GVHD
Grade III-IV Acute GVHD at Day 100
|
10.9 percentage of participants
Interval 4.0 to 21.3
|
—
|
|
Percentage of Participants With Grade II-IV and Grade III-IV Acute GVHD
Grade III-IV Acute GVHD at 6 Months
|
17.4 percentage of participants
Interval 8.1 to 29.7
|
—
|
SECONDARY outcome
Timeframe: 1 year post-transplantChronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=46 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
|
|---|---|---|
|
Number of Participants With Chronic GVHD
None
|
34 Participants
|
—
|
|
Number of Participants With Chronic GVHD
Mild
|
10 Participants
|
—
|
|
Number of Participants With Chronic GVHD
Severe
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: 1 year post-transplantChronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.
Outcome measures
| Measure |
Hematopoietic Stem Cell Transplant
n=46 Participants
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
Other Primary Immune Deficiencies (PID)
|
|---|---|---|
|
Percentage of Participants With Chronic GVHD
|
26.7 percentage of participants
Interval 14.6 to 40.4
|
—
|
Adverse Events
Hematopoietic Stem Cell Transplant
Serious events: 14 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Hematopoietic Stem Cell Transplant
n=46 participants at risk
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Hematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.
* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10
* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4
* Melphalan 140mg/m2 on Day -3
The GVHD prophylaxis will consist of the following:
* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.
* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
Cardiac disorders
Cardiac arrest
|
4.3%
2/46 • Number of events 2 • 1 year post-transplant
|
|
Cardiac disorders
Ventricular hypertrophy
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
General disorders
Death
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
Immune system disorders
Serum sickness
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
Infections and infestations
Sepsis
|
4.3%
2/46 • Number of events 2 • 1 year post-transplant
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Post transplant lymphoproliferative disorders
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
Nervous system disorders
Cerebrovascular accident
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
Nervous system disorders
Haemorrhagic stroke
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
Renal and urinary disorders
Proteinuria
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.3%
2/46 • Number of events 2 • 1 year post-transplant
|
|
Vascular disorders
Hypotension
|
2.2%
1/46 • Number of events 1 • 1 year post-transplant
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place