primary myelofibrosis MedDRA version: 20.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: allogeneic HSC
Product Code: allogeneic HSC
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Allogene HSC
Other descriptive name: Allogene HSC
Concentration unit: log10/ml
Sponsors
University Medical Center Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Symptomatic primary myelofibrosis or myelofibrosis post polycythaemia vera or essential thrombocythemia stage intermediate 2- or high-risk according to IPSS or DIPSS [46] or inter-mediate 1-risk with high risk cytogenetics, other than normal karyotype, sole del 20q, del 13q, or sole +9, or transfusion-dependency 2. Patients age: 18 - 70 years at time of inclusion (female and male) 3. Patients understand and voluntarily sign an informed consent form 4. Platelet count = 50 x 109/L 5. No prior Ruxolitinib treatment 6. ECOG = 2 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: 1. Severe renal, hepatic, pulmonary or cardiac disease, such as: • Total bilirubin, SGPT or SGOT > 3 times upper the normal level • Left ventricular ejection fraction < 30 % • Creatinine clearance < 30 ml/min • DLCO < 35 % and/or receiving supplementary continuous oxygen 2. Positive serology for HIV 3. Pregnant or lactating women (positive serum pregnancy test) 4. Age < 18 and = 71 years. 5. Uncontrolled invasive fungal infection at time of screening (baseline) 6. Serious psychiatric or psychological disorders 7. Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment 8. Transformation to AML
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare efficacy in terms of event free survival of allogeneic SCT for patients with myelofibrosis who have a suitable stem cell donor after a 3 months Ruxolitinib induction therapy with patients who lack a suitable stem cell donor and will continue to receive Ruxolitinib;Secondary Objective: To assess and compare the safety and efficacy of study treatments/ induction therapy in both study arms on spleen reduction, improvement of constitutional symptoms, QOL, toxicity, fibrosis regression, development of GvHD as well as chimerism, engraftment, relapse incidence, disease related mortality outcome and overall survival.;Primary end point(s): Event free survival (EFS) at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suitable donor;Timepoint(s) of evaluation of this end point: Ruxolitinib continuous therapy: every second months within the first year and following every third month up to 36 months. Allogeneic SCT: after 30 and 100 days after allo-SCT following every six months up to 36 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival at 3 years after allogeneic SCT compared to Ruxolitinib continuous therapy in patients without a suitable donor 2. Spleen reduction after 3 months of Ruxolitinib induction therapy 3. Improvement of constitutional symptoms (Loose of weight and night sweat) after 3 months Ruxolitinib induction therapy 4. Improvement of bone marrow fibrosis after 3 months of Ruxolitinib induction therapy 5. Incidence of acute graft-versus-host disease on Day +100 after allogeneic SCT according to the Glucksberg scale [ ] revised by Przepiorka et al. [ ] (Appendix 13.3) 6. Incidence of chronic graft-versus-host disease according to the NIH consensus criteria of Filipovich et al. [ ] (Appendix 13.4) at 1, 2 and 3 years after allogeneic SCT 7. Toxicity of Ruxolitinib scored according to NCI CTCAE, Version 4.0 (Appendix 13.2) 8. Toxicity of conditioning therapy scored according to NCI CTCAE, Version 4.0 (Appendix 13.2) 9. Cumulative incidence of relapse at 3 years after allogeneic SCT 10. Disease-related mortality at 3 years after allogeneic SCT and Ruxolitinib continuous thera-pies 11. Non-relapsed mortality at 1 and 3 years after allogeneic SCT and Ruxolitinib continuous therapy 12. Discontinuation rate at 3 years after Ruxolitinib continuous therapy (End of study) 13. Evaluation of Sorror Risk Score (see Appendix 13.1) on outcome after allogeneic SCT 14. Impact of chimerism on relapse incidence after allogeneic SCT 15. Evaluation of bone marrow fibrosis regression after allogeneic SCT at 30d, 100d, 1 year and 3 years 16. Evaluation of bone marrow fibrosis regression after Ruxolitinib continuous therapies at 30d, 100d, 1 year and 3 years 17. Evaluation of QOL (FACT-BMT) and QOL (MPN) before Ruxolitinib induction therapy (= baseline), at transplantation, and after transplantation at 6m, 1 year, 2 years and 3 years 18. Evaluation of QOL (FACT-BMT) and QOL (MPN) before Ruxolitinib induction therapy (= baseline), at confinement to Ruxolitini | — |
Countries
Germany
Contacts
Public ContactNicolaus Kröger
University Medical Center Hamburg-Eppendorf
Outcome results
None listed