Adult T-cell Leukemia/Lymphoma, Cutaneous T Cell Lymphoma, Graft Versus Host Disease, Lymphoma, T-Cell, Peripheral T Cell Lymphoma, Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, T-cell Lymphoma, T-cell Prolymphocytic Leukemia
Conditions
Keywords
stem cell transplant, graft versus host disease, lymphoma, leukemia
Brief summary
This phase II trial tests how well ruxolitinib as a maintenance medication works to prevent relapse and graft-versus-host disease (GVHD) for patients who have undergone stem cell transplantation for T-cell lymphoma. GVHD is a common problem that may occur after a blood stem cell transplant. The "graft" is the donor blood cells that patients get during the transplant. The "host" is the person receiving the cells. GVHD is when the donor graft attacks and damages some of the transplant recipient's tissues. Ruxolitinib is a type of drug called a Janus kinase (JAK) inhibitor which works by decreasing the immune response of cells in the body. It is also a cancer growth blocker that blocks the growth factors that trigger the cancer cells to divide and grow. Ruxolitinib works by blocking a gene, called JAK2, that is important in the production of cancer cells.
Detailed description
PRIMARY OBJECTIVES: I. Determine the effect of ruxolitinib phosphate (ruxolitinib) on relapse at 1-year after autologous (auto) stem cell transplant (SCT) in T-cell lymphoma (TCL). II. Determine the effect of ruxolitinib on graft versus host disease (GvHD) and relapse free-survival (GRFS) at 1-year for allogeneic (allo) SCT in TCL. SECONDARY OBJECTIVES: PRIMARY OBJECTIVES: I. Determine the effect of ruxolitinib phosphate (ruxolitinib) on relapse at 1-year after autologous (auto) stem cell transplant (SCT) in T-cell lymphoma (TCL). II. Determine the effect of ruxolitinib on graft versus host disease (GvHD) and relapse free-survival (GRFS) at 1-year for allogeneic (allo) SCT in TCL. SECONDARY OBJECTIVES: I. Survival (progression free survival \[PFS\]/overall survival \[OS\]) of patients with ruxolitinib maintenance (auto-SCT, allo-SCT, whole cohort). II. Determine the safety and feasibility of ruxolitinib maintenance post-SCT. III. Determine the effect of ruxolitinib on the cumulative incidence (CI) of grade II-IV acute GVHD (alloSCT), chronic extensive GVHD, non-relapse mortality (NRM) (auto-SCT and allo-SCT). EXPLORATORY OBJECTIVES: I. Determine the effect of maintenance ruxolitinib compared to matched historical controls using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. II. Determine the effect of ruxolitinib on immune modulation and reconstitution post-allo-SCT and upon disease relapse. OUTLINE: Starting day +35 to day +120 post-SCT, patients receive ruxolitinib orally (PO) twice daily (BID) on days 1-30 of each cycle. Cycles repeat every 30 days for 1 year post-SCT, in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET)-computed tomography (CT) scan and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or tissue biopsy throughout the study, at time of progression. After completion of study treatment, patients are followed up at 18 and 24 months then yearly until 5 years and at progression.
Interventions
DRUGRuxolitinib
Administered orally twice daily
Undergo PET-CT Scan
PROCEDUREBone Marrow Biopsy
Undergo bone marrow biopsy
PROCEDUREBiopsy Procedure
Undergo tissue biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
Sponsors
Jonathan Brammer
Incyte Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients with T-cell lymphoma \[PTCL (all subtypes), T-PLL, ATLL, and CTCL (all subtypes)\] in partial or complete remission between day +35 and +120 from auto-SCT or allo-SCT 2. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less 3. Adequate hematologic function defined by absolute neutrophil count (ANC) \> 1000/mm3 without granulocyte colony-stimulating factor (G-CSF) for at least 3 days, platelets \> 50K/mm3 without transfusion for at least 3 days and hemoglobin (Hb) \> 8.0 g/dL without transfusion for at least 3 days. 4. Adequate organ function defined by total Bilirubin \< 1.5 x ULN, alanine aminotransferase (ALT) \</= 3 x ULN, CKD-EPI eGFR ≥ 30 ml/min, SpO2 \> 92% without supplemental oxygen. 5. Able to tolerate oral or enteral medications. 6. Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study. 7. Able to read and sign informed consent.
Exclusion criteria
1. Anaplastic lymphoma kinase (ALK)+ or Dual specificity 22 (DUSP22)+ ALCL with low international prognostic index (IPI) score (\<2) in first complete remission. 2. Progressive disease or any other systemic therapy post-SCT (radiation allowed) 3. Disease progression to Ruxolitinib previously 4. GvHD requiring systemic therapy. 5. Active uncontrolled infections. 6. Active thrombotic active microangiopathy requiring therapy. 7. History of veno-occlusive disorder post-transplant 8. Use of platelets antiaggregant or anticoagulants deemed to be unsafe to be held in case of thrombocytopenia. 9. History of life-threatening bleeding defined as any bleeding that required invasive procedures or involving central nervous system. 10. Pregnancy (positive Beta HCG test in a woman with childbearing potential defined as not postmenopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women. 11. Uncontrolled Hepatitis B/C, HIV, tuberculosis, mycobacterium, or fungal infection. 12. Exposure to other investigational drugs within 4 weeks before enrollment. 13. Grade ≥ 3 non-hematologic toxicity from SCT that has not resolved to grade ≤ 2. 14. Myocardial infarction or stroke within 1 year of study entry. 15. Any uncontrolled medical problem at the discretion of the investigator that would pose a risk to the patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence (CI) of relapse | at 1-year post-auto-SCT | Relapse is defined as evidence of disease progression or recurrence based on Lugano criteria or confirmed by biopsy. |
| GvHD and relapse free-survival (GRFS) | at 1-year post-allo-SCT | GRFS is a composite endpoint of survival without grade III-IV acute GVHD, systemic therapy-requiring chronic GVHD (cGVHD), relapse, or death. Will be evaluated using the Kaplan-Meier method, with median survival and probability of surviving to relevant time points reported with point estimates and 90% confidence intervals separately for each study cohort. Comparisons to Center for International Blood and Marrow Transplant Research (CIBMTR) patients will use log-rank tests. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free survival (PFS) | At 1 and 2 years | Will be evaluated using the Kaplan-Meier method, with median survival and probability of surviving to relevant time points reported with point estimates and 90% confidence intervals separately for each study cohort. Comparisons to CIBMTR patients will use log-rank tests |
| Overall Survival (OS) | At 1 and 2 years | Will be evaluated using the Kaplan-Meier method, with median survival and probability of surviving to relevant time points reported with point estimates and 90% confidence intervals separately for each study cohort. Comparisons to CIBMTR patients will use log-rank tests. |
| Cumulative incidence of grade II-IV acute GVHD (allo-SCT cohort) | Up to 5 years | Will be conducted using non-relapse mortality (NRM) as a competing risk, with estimates of cumulative incidence at various time points reported with 90% confidence intervals. Cumulative incidences will be compared to CIBMTR data using Fine-Gray analysis. |
| Cumulative incidence of chronic extensive GvHD (allo-SCT cohort) | at 1 year post-SCT | Will be conducted using NRM as a competing risk, with estimates of cumulative incidence at various time points reported with 90% confidence intervals. Cumulative incidences will be compared to CIBMTR data using Fine-Gray analysis. |
| Cumulative Incidence of non-relapse mortality (NRM) at 1-year after (auto-SCT, allo-SCT, whole cohort) | At 1 year | Will be conducted using NRM as a competing risk, with estimates of cumulative incidence at various time points reported with 90% confidence intervals. Cumulative incidences will be compared to CIBMTR data using Fine-Gray analysis |
| Rates of grade 3-4 treatment Emergent Adverse Events | Up to 2 years | Treatment-emergent adverse events of grade 3 and higher will also be reported for each cohort |
| Rate of patients completing 1-year post-SCT maintenance Ruxolitinib | At 1 year post-SCT | Will be conducted using NRM as a competing risk, with estimates of cumulative incidence at various time points reported with 90% confidence intervals. Cumulative incidences will be compared to CIBMTR data using Fine-Gray analysis |
Countries
United States
Contacts
CONTACTThe Ohio State University Comprehensive Cancer Center
PRINCIPAL_INVESTIGATORJonathan Brammer, MD
Ohio State University Comprehensive Cancer Center
Outcome results
None listed