Adult patiens after allogeneic stem cell transplantation MedDRA version: 19.1 Level: LLT Classification code 10018653 Term: Graft-versus-host disease System Organ Class: 100000004870 MedDRA version: 19.1 Level: LLT Classification code 10067859 Term: Allogenic stem cell transplantation System Organ Class: 100000004865
Conditions
Interventions
Trade Name: Ninlaro
Product Name: Ixazomib
Pharmaceutical Form: Capsule
INN or Proposed INN: IXAZOMIB
CAS Number: 1072833-77-2
Other descriptive name: IXAZOMIB
Concentration unit: mg milligram(s)
Conc
Sponsors
Fundación Pública Andaluza para la Gestión en Salud de Sevilla (FISEVI)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients 18 years or older. 2. Patients having received reduced intensity conditioning (RIC) peripheral blood allogeneic stem cell transplantation. 3. Patients undergoing hematopoietic stem cell transplant from a matched or a single mismatched related or unrelated donor as definition accepted by protocol. 4. Patients receiving GVHD prophylaxis with sirolimus and tacrolimus and on stable levels during the last 2 weeks before inclusion. 5. Voluntary written consent must be given before performance of any study related procedure. 6. Female patients who accomplish with requisitions for not possibility of pregnancy (menopausia, effective methods of contraception), as detailed by protocol. 7. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2. 8. Patients must meet the following clinical laboratory criteria: • Absolute neutrophil count (ANC) 1,000/mm3 and platelet count 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. • Total bilirubin 1.5 the upper limit of the normal range (ULN). • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 ULN. • Calculated creatinine clearance 30 mL/min (see Section 11.2). 9. Ability to swallow and tolerate oral medication. 10. Absence of gastrointestinal symptoms that precludes oral intake and absorption. 11. Off antibiotics and amphotericin B formulations, voriconazole or other anti-fungal therapy for the treatment of active proven, probable or possible infections. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 124 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Female patients who are lactating or have a positive serum pregnancy test during the screening period. 2. Major surgery within 14 days before enrollment. 3. Central nervous system involvement with malignant cells. 4. Uncontrolled infection within 14 days before study enrollment. 5. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. 6. Systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort. 7. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 8. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol. 9. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. 10. Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 11. Patient has Grade 1 peripheral neuropathy. 12. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial. 13. Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not. 14. Active Graft versus host disease at the time of inclusion: patients are allowed to be included if acute GVHD is in complete remission and are receiving systemic steroids at < 0.25 mg / kg. 15. Active hematologic malignancy at the time of inclusion. 16. Active microangiopathy at the time of inclusion (according to IWG criteria) 17. Gastrointestinal disease or procedure than can interfere with oral absortion , intolerance to the ixazomib or difficulty to swallow.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To identify the optimal dose and to evaluate the safety profile of ixazomib in combination with sirolimus and tacrolimus in patients undergoing allogeneic stem cell transplantation. Phase II: To evaluate the efficacy of ixazomib in combination with sirolimus and tacrolimus to reduce the risk of moderate or severe chronic graft-versus-host disease (cGVHD) after 1 year postransplant.;Secondary Objective: Phase I: -To evaluate the efficacy of ixazomib in combination with sirolimus and tacrolimus in terms of incidence of moderate or severe chronic GVHD according to NIH scale after 9 months postransplant. -To evaluate the effect of ixazomib on immune response as compared to a control group of patients receiving sirolimus and tacrolimus. Phase II: -To evaluate the effect of ixazomib in combination with sirolimus and tacrolimus on the incidence of moderate or severe GVHD after 2 years postransplant. -To evaluate the effect of ixazomib in combination with sirolimus and tacrolimus on GVHD free survival and relapse-free GVHD-free survival as compared to a control group after 1 and 2 years postransplant. -To evaluate the effect of ixazomib in combination with sirolimus and tacrolimus on the immune response after transplantation -To describe the exposure to immunosuppressive treatment at 1 and 2 years postransplant. -Overall and disease free survival at 2 years postransplant.;Primary end point(s): Phase I: -To identify the optimal dose and evaluate the safety of ixazomib used after transplantation. -To evaluate the efficacy of ixazomib used after transplantation, measured in terms of risk of moderate or severe GVHD according to NIH scale. -To evaluate the immune recovery of the 12 patients included in the safety expansion cohort and compare it with a cohort of 12 patients receiving sirolimus and tacrolimus out of the trial. Phase II. -To evaluate the reduction of risk of moderate or severe GVHD according to NIH scale;Timepoint(s) of evaluation of th | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I study: -To evaluate the risk of moderate or revere cGVHD according to NIH scale at 2 years postrasplantation,this is, 6 months after ixazomib discontinuation. -To evaluate the effect of ixazomib on cGVHD free survival -To evaluate the immune recovery after transplantation among patients exposed or not to ixazomib. -To describe exposure to immunosuppressive treatment at 1 and 2 years postransplant. -To describe the overall and disease free survival at 2 years postransplant among patients exposed or not to ixazomib.;Timepoint(s) of evaluation of this end point: 1 and 2 years postransplant. | — |
Countries
Spain
Contacts
Public ContactUICEC-HUVR
Unidad de Investigación Clínica y ensayos Clínicos
Outcome results
None listed