Malignant Neoplasm
Conditions
Brief summary
This phase II trial studies donor atorvastatin treatment for the prevention of severe acute graft-versus-host disease (GVHD) in patients undergoing myeloablative peripheral blood stem cell (PBSC) transplantation. Giving chemotherapy and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also prevent the patient's immune system reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving atorvastatin to the donor before transplant may prevent this from happening.
Detailed description
PRIMARY OBJECTIVES: I. To assess whether 2 weeks of donor statin treatment reduces the risk of severe acute GVHD. SECONDARY OBJECTIVES: I. To assess whether 2 weeks of statin treatment of normal PBSC donors is feasible, tolerable and safe. OUTLINE: Donors receive atorvastatin orally (PO) beginning on day -14 and continuing until the last day of stem cell collection.
Interventions
PROCEDUREAllogeneic Hematopoietic Stem Cell Transplantation
Undergo myeloablative allogeneic PBSC transplant
DRUGAtorvastatin Calcium
Given PO
PROCEDUREPeripheral Blood Stem Cell Transplantation
Undergo myeloablative allogeneic PBSC transplant
Sponsors
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Human leukocyte antigen (HLA)-identical sibling donor * Myeloablative preparative regimen (i.e., \>= TBI 12.0 Gy, \>= busulfan (BU) 8.0 mg/kg PO, \>= BU 6.4 mg/kg intravenously (IV), \>= treosulfan 42 g/m\^2 IV) according to investigational study or standard treatment plan; other myeloablative preparative regimens are acceptable as long as they are approved by the principal investigator or designee * Transplantation of PBSC * Cyclosporine (CSP)-based postgrafting immunosuppression * Willingness to give informed consent * DONOR: Age \>= 18 years * DONOR: HLA genotypically identical sibling * DONOR: Willingness to give informed consent
Exclusion criteria
* Nonmyeloablative preparative regimen * Participation in an investigational study that has acute GVHD as the primary endpoint * The allogeneic PBSC donor has a contraindication to statin treatment * DONOR: Age \< 18 years * DONOR: Active liver disease (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] levels \> 2 times the upper limit of normal \[ULN\]) * DONOR: History of myopathy * DONOR: Hypersensitivity to atorvastatin * DONOR: Pregnancy * DONOR: Nursing mother * DONOR: Current serious systemic illness * DONOR: Concurrent treatment with strong inhibitors of hepatic cytochrome P450 (CYP) 3A4 (i.e. clarithromycin, erythromycin, protease inhibitors, azole antifungals) * DONOR: Current use of statin drug * DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) or local criteria for stem cell donation * DONOR: Total creatinine kinase \> 2 times the ULN
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grade 3-4 Acute GVHD | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival | 1 year after transplant | Evaluated as Kaplan-Meier estimate in the patients/recipients. |
| Grades II-IV Acute GVHD | 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. |
| Non-relapse Mortality | At day 100 | Cumulative incidence rate of non-relapse mortalities, assessed at day 100 in the patients/recipients. |
| Chronic Extensive GVHD | 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. |
| Proportion of Donors Who Have to Discontinue Atorvastatin Because of Toxicity | Until completion of stem cell collection (on average 14 days) | — |
| Proportion of Patients Requiring Secondary Systemic Immunosuppressive Therapy | First 100 days after transplant | — |
| Recurrent or Progressive Malignancy | 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. |
| Overall Survival | 1 year after transplant | Determined and presented as Kaplan-Meier estimates, assessed at 1 year in the patients/recipients. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 38 |
| Patients Recipients of donor stem cells. | 38 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Change in recipient treatment plan | 2 | 2 |
| Overall Study | Delay in Transplant | 1 | 0 |
| Overall Study | Transplant was delayed | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Patients | Total | Donors |
|---|---|---|---|
| Age, Continuous | 52 years | 53 years | 54 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) White | 27 Participants | 55 Participants | 28 Participants |
| Sex: Female, Male Female | 16 Participants | 33 Participants | 17 Participants |
| Sex: Female, Male Male | 22 Participants | 43 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 38 | 0 / 41 |
| serious Total, serious adverse events | 21 / 38 | 0 / 41 |
Outcome results
Primary
Grade 3-4 Acute GVHD
Cumulative incidence rate of grade 3-4 acute GVHD with death as a completing risk, assessed at day 100 in the patients/recipients.
Time frame: First 100 days after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients | Grade 3-4 Acute GVHD | 0.21 probability |
Secondary
Chronic Extensive GVHD
Cumulative incidence rate of chronic extensive GVHD with death as a competing risk, assessed at 2 years in the patients/recipients.
Time frame: 2 years post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients | Chronic Extensive GVHD | 0.51 probability |
Secondary
Disease-free Survival
Evaluated as Kaplan-Meier estimate in the patients/recipients.
Time frame: 1 year after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients | Disease-free Survival | 0.47 disease free survival probability |
Secondary
Grades II-IV Acute GVHD
Cumulative incidence rate of grades II-IV acute GVHD with death as a competing risk, assessed at 100 days in the patients/recipients.
Time frame: First 100 days after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients | Grades II-IV Acute GVHD | 0.78 probability |
Secondary
Non-relapse Mortality
Cumulative incidence rate of non-relapse mortalities, assessed at one year in the patients/recipients.
Time frame: At 1 year after HCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients | Non-relapse Mortality | 0.29 probability |
Secondary
Non-relapse Mortality
Cumulative incidence rate of non-relapse mortalities, assessed at day 100 in the patients/recipients.
Time frame: At day 100
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients | Non-relapse Mortality | 0.13 probability |
Secondary
Overall Survival
Determined and presented as Kaplan-Meier estimates, assessed at 1 year in the patients/recipients.
Time frame: 1 year after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients | Overall Survival | 0.55 survival probability |
Secondary
Proportion of Donors Who Have to Discontinue Atorvastatin Because of Toxicity
Time frame: Until completion of stem cell collection (on average 14 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients | Proportion of Donors Who Have to Discontinue Atorvastatin Because of Toxicity | 3 Participants |
Secondary
Proportion of Patients Requiring Secondary Systemic Immunosuppressive Therapy
Time frame: First 100 days after transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients | Proportion of Patients Requiring Secondary Systemic Immunosuppressive Therapy | 5 Participants |
Secondary
Recurrent or Progressive Malignancy
Cumulative incidence rate of recurrent or progressive malignancy with death as a competing risk, assessed at 3 years in the patients/recipients.
Time frame: Up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients | Recurrent or Progressive Malignancy | 0.27 probability |