Allogeneic hematopoietic stem cell transplantation (HTC) is the only curative option for many patients with hematologic malignancies but \>50% of this patients will develop extensive chronic graft-versus-host disease (cGVHD), which remains the most important complication after HTC. Classically, the most effective strategies to prevent GVHD have not improved survival; therefore, the new strategies are being sought. This study is designed in two phases: the main objective for phase I study is the more suitable dose for ixazomib search. Phase II study is designed to evaluate the efficacy of ixazomib at the doses stablished in phase I.
The study design is based on a phase I / II trial in eight Spanish hospitals. In the phase I, a number of 3 to 12 patients will be included to evaluate the optimal dose of ixazomib in combination with sirolimus and tacrolimus. In the phase II, a total number of 130 patients will be randomized to receive ixazomib or the best medical recommendation added in order to evaluate the efficacy of ixazomib. This patients who will receive any prophylaxis for GVHD, except those patients who received antithymocyte globulin , cyclophosphamide or any T depletion protocol in vitro or in vivo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
142
Ixazomib capsules. Phase I: Starting dose of Ixazomib: 3.0 or 4.0 mg by day +1, +8 and +15. Phase II: Starting Dose of Ixazomib: Maximum tolerated dose from Phase I.
Tacrolimus at dose of 0.02 mg/kg/day and then 0.06 mg/kg/day.
Sirolimus oral solution. Standing 6 mg orally on day -5 and continued 4mg per day. This drugs should be slowly tapered starting 3 months posttransplant in order to stop them at 9 to 12 months posttransplant according to physician criteria.
Except antithymocyte globulin, cyclophosphamide or any T depletion protocol in vitro or in vivo.
ICO- Hospital Germans Trias i Pujol
Badalona, Spain
Hospital Clinic de Barcelona
Barcelona, Spain
Hospital de la Santa Creu I Sant Pau
Barcelona, Spain
Hospital Universitario Vall D´Hebrón
Barcelona, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Hospital Clinico Universitario Salamanca
Salamanca, Spain
Hospital Universitario Virgen del Rocío
Seville, Spain
Hospital Clínico Universitario de Valencia
Valencia, Spain
Maximun tolerated dose
Maximun tolerated dose of the ixazomib in combination with sirolimus and tacrolimus in patients following allogeneic stem cell transplantation for the phase I study will be determinated
Time frame: 3 months after transplantation (a total of 3 cycles of 28 days length of study treatment)
Efficacy of ixazomib for phase II study
Presence of moderate plus severe Chronic Graft-versus-host Disease according to NIH scale in patients receiving the maximum tolerated dose.
Time frame: 9 months after transplantation (a total of 9 cycles of 28 days length of study treatment)
Event immune recovery for the phase I study
Quantification of time of event immune recovery in patients exposed and not exposed to ixazomib.
Time frame: The post-transplant days +180, +270, +365, +545, +730
Event free survival for phase II study.
Quantification of time of event free survival for patients receiving the maximum tolerated dose.
Time frame: Just after the time of transplantation and 1 and 2 years after transplantation
Event immune recovery for phase II study.
Quantification of time of event immune recovery in patients exposed and not exposed to ixazomib.
Time frame: The post-transplant days +180, +270, +365, +545, +730
Exposure to immunosuppressive treatment for phase II study.
Evaluation of needs of additional permitted immunosuppressive treatment administered as concomitant medication
Time frame: 1 and 2 years after transplantation.
Overall disease free survival for phase II study
Quantification of time of overall survival after study treatment
Time frame: 2 years after transplantation.
Serious adverse event for phase II study
Describe the serious adverse event notified during the study
Time frame: 1 and 2 years after transplantation
Risk of moderate or severe GVHD for phase II study
To evaluate the risk of moderate or severe GVHD according to the NIH scale
Time frame: 2 years after transplantation
Differences among patients receiving a reduced-intensity and myeloablative conditioning regimen for phase II study.
To evaluate differences in terms of chronic GVHD and treatment tolerance
Time frame: 1 and 2 years after transplantation
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