Trial Outcomes & Findings for Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Myeloablative Peripheral Blood Stem Cell Transplantation (NCT NCT01525407)

NCT ID: NCT01525407

Last Updated: 2017-08-17

Results Overview

Cumulative incidence rate of grade 3-4 acute GVHD with death as a completing risk, assessed at day 100 in the patients/recipients.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 83 participants
• Primary outcome timeframe: First 100 days after transplant
• Results posted on: 2017-08-17

Participant Flow

Participant milestones

Measure	Donors Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection. Allogeneic Hematopoietic Stem Cell Transplantation: Undergo myeloablative allogeneic PBSC transplant Atorvastatin Calcium: Given PO Peripheral Blood Stem Cell Transplantation: Undergo myeloablative allogeneic PBSC transplant	Patients Recipients of donor stem cells.
Overall Study STARTED	41	42
Overall Study COMPLETED	38	38
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Measure	Donors Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection. Allogeneic Hematopoietic Stem Cell Transplantation: Undergo myeloablative allogeneic PBSC transplant Atorvastatin Calcium: Given PO Peripheral Blood Stem Cell Transplantation: Undergo myeloablative allogeneic PBSC transplant	Patients Recipients of donor stem cells.
Overall Study Change in recipient treatment plan	2	2
Overall Study Withdrawal by Subject	0	1
Overall Study Transplant was delayed	0	1
Overall Study Delay in Transplant	1	0

Baseline Characteristics

Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Myeloablative Peripheral Blood Stem Cell Transplantation

Baseline characteristics by cohort

Measure	Donors n=38 Participants Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection. Allogeneic Hematopoietic Stem Cell Transplantation: Undergo myeloablative allogeneic PBSC transplant Atorvastatin Calcium: Given PO Peripheral Blood Stem Cell Transplantation: Undergo myeloablative allogeneic PBSC transplant	Patients n=38 Participants Recipients of donor stem cells.	Total n=76 Participants Total of all reporting groups
Age, Continuous	54 years n=5 Participants	52 years n=7 Participants	53 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	22 Participants n=7 Participants	43 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	4 Participants n=5 Participants	4 Participants n=7 Participants	8 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	27 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: First 100 days after transplant

Cumulative incidence rate of grade 3-4 acute GVHD with death as a completing risk, assessed at day 100 in the patients/recipients.

Outcome measures

Measure	Patients n=38 Participants Recipients of donor stem cells.
Grade 3-4 Acute GVHD	0.21 probability Interval 0.1 to 0.35

SECONDARY outcome

Timeframe: 2 years post transplant

Cumulative incidence rate of chronic extensive GVHD with death as a competing risk, assessed at 2 years in the patients/recipients.

Outcome measures

Measure	Patients n=38 Participants Recipients of donor stem cells.
Chronic Extensive GVHD	0.51 probability Interval 0.33 to 0.66

SECONDARY outcome

Timeframe: 1 year after transplant

Evaluated as Kaplan-Meier estimate in the patients/recipients.

Outcome measures

Measure	Patients n=38 Participants Recipients of donor stem cells.
Disease-free Survival	0.47 disease free survival probability Interval 0.34 to 0.66

SECONDARY outcome

Timeframe: First 100 days after transplant

Cumulative incidence rate of grades II-IV acute GVHD with death as a competing risk, assessed at 100 days in the patients/recipients.

Outcome measures

Measure	Patients n=38 Participants Recipients of donor stem cells.
Grades II-IV Acute GVHD	0.78 probability Interval 0.61 to 0.89

SECONDARY outcome

Timeframe: At day 100

Cumulative incidence rate of non-relapse mortalities, assessed at day 100 in the patients/recipients.

Outcome measures

Measure	Patients n=38 Participants Recipients of donor stem cells.
Non-relapse Mortality	0.13 probability Interval 0.05 to 0.26

SECONDARY outcome

Timeframe: At 1 year after HCT

Cumulative incidence rate of non-relapse mortalities, assessed at one year in the patients/recipients.

Outcome measures

Measure	Patients n=38 Participants Recipients of donor stem cells.
Non-relapse Mortality	0.29 probability Interval 0.15 to 0.44

SECONDARY outcome

Timeframe: 1 year after transplant

Determined and presented as Kaplan-Meier estimates, assessed at 1 year in the patients/recipients.

Outcome measures

Measure	Patients n=38 Participants Recipients of donor stem cells.
Overall Survival	0.55 survival probability Interval 0.42 to 0.74

SECONDARY outcome

Timeframe: Until completion of stem cell collection (on average 14 days)

Outcome measures

Measure	Patients n=41 Participants Recipients of donor stem cells.
Proportion of Donors Who Have to Discontinue Atorvastatin Because of Toxicity	3 Participants

SECONDARY outcome

Timeframe: First 100 days after transplant

Outcome measures

Measure	Patients n=38 Participants Recipients of donor stem cells.
Proportion of Patients Requiring Secondary Systemic Immunosuppressive Therapy	5 Participants

SECONDARY outcome

Timeframe: Up to 3 years

Cumulative incidence rate of recurrent or progressive malignancy with death as a competing risk, assessed at 3 years in the patients/recipients.

Outcome measures

Measure	Patients n=38 Participants Recipients of donor stem cells.
Recurrent or Progressive Malignancy	0.27 probability Interval 0.14 to 0.42

Adverse Events

Patient Adverse Events

Serious events: 21 serious events

Other events: 0 other events

Deaths: 0 deaths

Donor Adverse Events

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Patient Adverse Events n=38 participants at risk Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	Donor Adverse Events n=41 participants at risk Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier.
Respiratory, thoracic and mediastinal disorders DAH	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
General disorders Multi-Organ Failure	5.3% 2/38 • Number of events 2 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Infections and infestations Fever/Infection	23.7% 9/38 • Number of events 11 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Metabolism and nutrition disorders Metabolic Acidosis	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Gastrointestinal disorders Pneumotosis	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Renal and urinary disorders Acute Kidney Injury	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Respiratory, thoracic and mediastinal disorders Pulmonary Emboli	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Immune system disorders GVHD	18.4% 7/38 • Number of events 8 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Blood and lymphatic system disorders Relapse	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Respiratory, thoracic and mediastinal disorders IPS	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Blood and lymphatic system disorders Bleeding	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Respiratory, thoracic and mediastinal disorders ARDS	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Gastrointestinal disorders Nausea/Vomiting	7.9% 3/38 • Number of events 3 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Vascular disorders Dehydration	2.6% 1/38 • Number of events 2 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Metabolism and nutrition disorders Hypercalcemia	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Musculoskeletal and connective tissue disorders Back Pain	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.
Immune system disorders EBV-PTLD	2.6% 1/38 • Number of events 1 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.	0.00% 0/41 • Donor: SAEs, AEs (≥ grade 2) and UPs will be monitored and recorded from the time the donor starts atorvastatin therapy through the time of discharge from the transplant center after donation of stem cells or 7 days after the discontinuation of the medication, whichever occurs earlier. Recipient: SAEs and UPs (life-threatening or fatal) will be monitored and recorded from the time the recipient starts conditioning therapy through day 100 or discharge from the center, whichever occurs earlier.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Marco Mielcarek

Fred Hutchinson Cancer Research Center

Phone: 2066672827

Email: mmielcar@fredhutch.org

Results disclosure agreements

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