Phase 2
N=47
Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies
Aggressive Non-Hodgkin Lymphoma · Blasts Under 5 Percent of Bone Marrow Nucleated Cells · Chronic Lymphocytic Leukemia · Loss of Chromosome 17p · Myelodysplastic/Myeloproliferative Neoplasm
Bottom Line
View on ClinicalTrials.gov: NCT01527045 ↗Enrolled (actual)
47
Serious AEs
2.2%
Results posted
Nov 2019
Primary outcome: Primary: Number of Patients With Grade III-IV Acute Graft-versus-host Disease (GVHD) Post-transplant — 2; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Atorvastatin Calcium (Drug); Cyclosporine (Drug); Fludarabine Phosphate (Drug); Laboratory Biomarker Analysis (Other); Mycophenolate Mofetil (Drug); Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation (Procedure); Peripheral Blood Stem Cell Transplantation (Procedure); Total-Body Irradiation (Radiation)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Fred Hutchinson Cancer Center
- Primary completion
- Oct 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Grade III-IV Acute Graft-versus-host Disease (GVHD) Post-transplant |
2; 0; 0 | — |
| SECONDARY Number of Patients With Grades II-IV Acute Graft-versus-host-disease (GVHD) |
15; 2; 6 | — |
| SECONDARY Number of Patients Requiring Secondary Systemic Immunosuppressive Therapy |
23; 3; 4 | — |
| SECONDARY Number of Patients With Chronic Extensive GVHD |
8; 1; 5 | — |
| SECONDARY Number of Patients With Recurrent or Progressive Malignancy |
7; 4; 3 | — |
| SECONDARY Number of Non-relapse Mortalities |
4; 1; 0 | — |
| SECONDARY Number of Patients Surviving Overall |
21; 3; 9 | — |
| SECONDARY Number of Donors Discontinuing Atorvastatin Due to Toxicity |
2; 0; 1 | — |
Summary
This phase II trial studies how well donor atorvastatin treatment works in preventing severe graft-versus-host disease (GVHD) after nonmyeloablative peripheral blood stem cell (PBSC) transplant in patients with hematological malignancies. Giving low doses of chemotherapy, such as fludarabine phosphate, before a donor PBSC transplantation slows the growth of cancer cells and may also prevent the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also cause an immune response against the body's normal cells (GVHD). Giving atorvastatin to the donor before transplant may prevent severe GVHD.
Eligibility Criteria
Inclusion Criteria
IF PROTOCOL 2546 SERVES AS AN ADJUNCT PROTOCOL, THE PATIENTS ONLY NEEDS TO MEET INCLUSION CRITERIA 1 THROUGH 5A
- Availability of human leukocyte antigen (HLA)-identical sibling donor
- Transplantation with PBSC
- CSP-based postgrafting immunosuppression
- Willingness to give informed consent
- Patient is enrolled on an investigational nonmyeloablative HCT protocol or a nonmyeloablative treatment plan with postgrafting CSP that does not use acute GVHD as its primary endpoint (protocol 2546 serves as adjunct protocol); OR
- Patient is not enrolled on an investigational nonmyeloablative HCT protocol, in which case protocol 2546 serves as an independent primary treatment protocol and the patient must meet the following inclusion and exclusion criteria:
- Patients must have a hematologic malignancy treatable by nonmyeloablative HCT; the following diseases will be permitted although other diagnoses can be considered if approved by Patient Care Conference (PCC) and the principal investigator:
- Aggressive non-Hodgkin lymphomas (NHL) and other histologies such as diffuse large B-cell NHL - not eligible for autologous HCT, not eligible for high-dose allogeneic HCT, or after failed autologous HCT
- Mantle-cell NHL - may be treated in first complete remission (CR); (diagnostic lumbar puncture [LP] required pre-transplant)
- Low grade NHL - with = 18 years
- DONOR: HLA genotypically identical sibling
- DONOR: Willingness to give informed consent
Exclusion Criteria
IF PROTOCOL 2546 SERVES AS AN ADJUNCT PROTOCOL, THE PATIENT ONLY NEEDS TO MEET EXCLUSION CRITERIA 1 THROUGH 3
- Myeloablative 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
- Patients eligible for and willing to receive potentially curative high-dose chemotherapy and autologous HCT
- Cardiac ejection fraction 3mg/dl, or actively symptomatic biliary disease
- Patients with renal failure are eligible; however, patients with pre-existing renal insufficiency will likely have further compromise in renal function and may require dialysis
- Patients who are seropositive for human immunodeficiency virus (HIV)
- Women who are pregnant or breast-feeding
- Fertile men or women unwilling to use contraception during HCT and for 12 months afterward
- Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
- Karnofsky score 2 times the ULN
Data sourced from ClinicalTrials.gov (NCT01527045). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.