Trial Outcomes & Findings for Study of Low-Intensity Conditioning for Allogeneic Stem Cell Transplant (NCT NCT00143845)
NCT ID: NCT00143845
Last Updated: 2017-03-08
Results Overview
The primary objective of this study was to establish the rate of acute GVHD following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. Glucksberg staging was used for organ grading of GVHD. Clinical GVHD was assessed as follows: Grade 0: No stage 1-4 of any organ Grade 1: Stage 1-2 rash and no liver or gut involvement Grade 2: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 GI Grade 3: Stage 0-3 skin with Stage 2-3 liver, or Stage 2-4 GI Grade 4: Stage 4 skin rash, or Stage 4 liver involvement
COMPLETED
PHASE2
54 participants
100 days
2017-03-08
Participant Flow
Participant milestones
| Measure |
Immunosuppression Taper
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
|
|---|---|
|
Overall Study
STARTED
|
54
|
|
Overall Study
COMPLETED
|
54
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Low-Intensity Conditioning for Allogeneic Stem Cell Transplant
Baseline characteristics by cohort
| Measure |
Immunosuppression Taper
n=45 Participants
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
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|---|---|
|
Age, Continuous
|
56 years
n=5 Participants
|
|
Gender
Female
|
22 Participants
n=5 Participants
|
|
Gender
Male
|
23 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 100 daysPopulation: 54 patients were enrolled however 9 patients did not receive planned donor lymphocyte infusion. 45 patients were analyzed.
The primary objective of this study was to establish the rate of acute GVHD following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. Glucksberg staging was used for organ grading of GVHD. Clinical GVHD was assessed as follows: Grade 0: No stage 1-4 of any organ Grade 1: Stage 1-2 rash and no liver or gut involvement Grade 2: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 GI Grade 3: Stage 0-3 skin with Stage 2-3 liver, or Stage 2-4 GI Grade 4: Stage 4 skin rash, or Stage 4 liver involvement
Outcome measures
| Measure |
Immunosuppression Taper
n=45 Participants
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
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|---|---|
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Percentage of Participants With Acute Graft Versus Host Disease (GVHD) Grades 2-4
|
73 percentage of participants
|
PRIMARY outcome
Timeframe: two yearsPopulation: 54 patients were enrolled however 9 patients did not receive planned donor lymphocyte infusion. 45 patients were analyzed.
The second primary objective was to determine the percentage of participants with progression free survival following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. We define disease progression as disease recurrence within 180 days of transplant.
Outcome measures
| Measure |
Immunosuppression Taper
n=45 Participants
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
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|---|---|
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Percentage of Participants With Progression Free Survival
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35 percentage of participants
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SECONDARY outcome
Timeframe: 2 YearsPopulation: 54 patients were enrolled however 9 patients did not receive planned donor lymphocyte infusion. 45 patients were analyzed.
To estimate the overall survival of patients progression following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies.
Outcome measures
| Measure |
Immunosuppression Taper
n=45 Participants
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
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|---|---|
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Percentage of Patients Alive at 2 Years
|
38 percentage of participants
|
Adverse Events
Immunosuppression Taper
Serious adverse events
| Measure |
Immunosuppression Taper
n=54 participants at risk
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
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|---|---|
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Gastrointestinal disorders
Diarrhea
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18.5%
10/54
|
|
Immune system disorders
GVHD
|
16.7%
9/54
|
|
Vascular disorders
DVT
|
1.9%
1/54
|
|
Infections and infestations
Infection
|
29.6%
16/54
|
|
General disorders
Primary Graft Failure
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1.9%
1/54
|
|
General disorders
Fever
|
9.3%
5/54
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Relapsed Disease
|
1.9%
1/54
|
|
Cardiac disorders
Hypotension
|
3.7%
2/54
|
|
Gastrointestinal disorders
Vomiting
|
7.4%
4/54
|
|
Ear and labyrinth disorders
Vertigo
|
1.9%
1/54
|
|
Nervous system disorders
Headache
|
1.9%
1/54
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
1.9%
1/54
|
|
General disorders
Weakness
|
1.9%
1/54
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
1.9%
1/54
|
|
General disorders
Pyrexia
|
3.7%
2/54
|
|
Gastrointestinal disorders
Nausea
|
7.4%
4/54
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
1.9%
1/54
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.9%
1/54
|
|
Nervous system disorders
Syncope
|
1.9%
1/54
|
|
Nervous system disorders
Seizure
|
1.9%
1/54
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.9%
1/54
|
|
Investigations
Lipase
|
1.9%
1/54
|
|
Investigations
Amylase
|
1.9%
1/54
|
|
Gastrointestinal disorders
Abdominal pain
|
7.4%
4/54
|
|
Cardiac disorders
Supraventricular tachycardia
|
1.9%
1/54
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
1.9%
1/54
|
|
Cardiac disorders
Supraventricular arrhythmia
|
1.9%
1/54
|
|
Immune system disorders
GVHD with infectious complications
|
1.9%
1/54
|
|
General disorders
Death
|
5.6%
3/54
|
Other adverse events
| Measure |
Immunosuppression Taper
n=54 participants at risk
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
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|---|---|
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Metabolism and nutrition disorders
Hypomagnesemia
|
42.6%
23/54
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
53.7%
29/54
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
11.1%
6/54
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
51.9%
28/54
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
11.1%
6/54
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
29.6%
16/54
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
25.9%
14/54
|
|
Metabolism and nutrition disorders
Hypokalemia
|
31.5%
17/54
|
|
Metabolism and nutrition disorders
Hyponatremia
|
37.0%
20/54
|
|
Metabolism and nutrition disorders
Hypernatremia
|
9.3%
5/54
|
|
Investigations
Creatinine
|
33.3%
18/54
|
|
Gastrointestinal disorders
Esophogitis
|
13.0%
7/54
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
44.4%
24/54
|
|
Investigations
AST
|
37.0%
20/54
|
|
Investigations
ALT
|
37.0%
20/54
|
|
Investigations
ALK
|
27.8%
15/54
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.3%
5/54
|
|
Infections and infestations
Infection
|
18.5%
10/54
|
|
Investigations
Total Bilirubin
|
18.5%
10/54
|
|
Gastrointestinal disorders
Mucositis
|
7.4%
4/54
|
|
Gastrointestinal disorders
Diarrhea
|
9.3%
5/54
|
Additional Information
Dr. John Levine, M.D.
University of Michigan Comprehensive Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place