Ixazomib in the Prophylaxis of Chronic Graft-versus-host Disease.

NCT03225417 | Active Not Recruiting Phase 1

• 1 other identifier: X16082
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Hematopoietic Stem Cell Transplantation; Multiple Myeloma

Keywords

Ixazomib

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  9 months after transplantation (a total of 9 cycles of 28 days length of study treatment)

Secondary Outcomes (8)

• Event immune recovery for the phase I study

  The post-transplant days +180, +270, +365, +545, +730

• Event free survival for phase II study.

  Just after the time of transplantation and 1 and 2 years after transplantation

• Event immune recovery for phase II study.

  The post-transplant days +180, +270, +365, +545, +730

• Exposure to immunosuppressive treatment for phase II study.

  1 and 2 years after transplantation.

• Overall disease free survival for phase II study

  2 years after transplantation.

Study Arms (2)

Experimental group

EXPERIMENTAL

Phase I: Ixazomib + Tacrolimus + Sirolimus. Ixazomib doses in this study is 3 to 4 mg of ixazomib on day +1, +8 and +15. Tacrolimus at a dose of 0.02 mg/kg/day and then 0.06 mg/kg/day. Sirolimus at a dose of 6 mg on day -5 and then 4 mg per day. Phase II: Ixazomib+ any prophylaxis for GVHD, except antithymocyte globulin, cyclophosphamide or any T depletion protocol in vitro or in vivo. Starting Dose of Ixazomib according to phase I.

Drug: Ixazomib; Drug: Tacrolimus; Drug: Sirolimus; Drug: Any prophylaxis for GVHD

Control group

OTHER

Any prophylaxis for GVHD, except antithymocyte globulin, cyclophosphamide or any T depletion protocol in vitro or in vivo.

Drug: Tacrolimus; Drug: Sirolimus; Drug: Any prophylaxis for GVHD

Interventions

Ixazomib DRUG

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.

Also known as: X16082

Experimental group

Tacrolimus DRUG

Tacrolimus at dose of 0.02 mg/kg/day and then 0.06 mg/kg/day.

Also known as: Prograf

Control group; Experimental group

Sirolimus DRUG

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.

Also known as: Rapamune

Control group; Experimental group

Any prophylaxis for GVHD DRUG

Except antithymocyte globulin, cyclophosphamide or any T depletion protocol in vitro or in vivo.

Also known as: Any prophylaxis for GVHD, except antithymocyte globulin, cyclophosphamide or any in vitro or in vivo.

Control group; Experimental group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18 years or older.
• Patients on the day +100 +/- 20 days who have received an allogeneic transplant with myeloablative or reduced intensity conditioning peripheral blood allogeneic stem cell transplantation.
• Patients who have received a hematopoietic bone marrow transplant hematopoietic progenitors of peripheral blood from histo / compatible donor as definition accepted by protocol.
• Patients receiving any prophylaxis for GVHD, except for antithymocyte globulin, cyclophosphamide or any in vitro or in vivo depletion protocol.
• Voluntary written consent must be given before performance of any study related procedure.
• Female patients who accomplish with requisitions for not possibility of pregnancy (menopausal, effective methods of contraception), as detailed by protocol.
• Eastern Cooperative Oncology Group performance status and/or other performance status 0, 1, or 2.
• Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count 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 .
• Alanine aminotransferase and aspartate aminotransferase 3 upper limit of the normal range.
• Calculated creatinine clearance 30 mL/min.
• Ability to swallow and tolerate oral medication.
• Absence of gastrointestinal symptoms that precludes oral intake and absorption.
• Off antibiotics and amphotericin B formulations, voriconazole or other anti-fungal therapy for the treatment of active proven, probable or possible infections.

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery within 14 days before enrollment.
• Central nervous system involvement with malignant cells.
• Uncontrolled infection within 14 days before study enrollment.
• 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.
• Systemic treatment, within 14 days before the first dose of ixazomib, with strong Cytochrome P450, family 3, subfamily A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
• Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus positive.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• 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.
• Patient has Grade 1 with pain or ≥ grade 2 with or without pain peripheral neuropathy.
• 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.
• Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.
• Gastrointestinal disease or procedure than can interfere with oral absorption , intolerance to the ixazomib or difficulty to swallow.

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead
• Spanish Clinical Research Network - SCReN: collaborator

Study Sites (8)

ICO- Hospital Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu I Sant Pau

Barcelona, Spain

Location

Hospital Universitario Vall D´Hebrón

Barcelona, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico Universitario Salamanca

Salamanca, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Related Publications (1)

• Caballero-Velazquez T, Delgado Serrano J, Lopez-Corral L, Ferra-Coll C, Garcia-Calderon CB, Valcarcel D, Garcia-Cadenas I, Perez Lopez E, Jimenez Lorenzo MJ, Martin-Dominguez FM, Jimenez-Leon MLR, Orti G, Escamilla Gomez V, Blazquez-Goni C, Cabero Martinez A, Andrade Ruiz H, Menendez-Pedregal E, Sanchez-Guijo F, Perez Simon JA. Ixazomib decreases the risk of chronic graft-versus-host disease: identification of cGVHD biomarkers. Blood Adv. 2025 Nov 11;9(21):5528-5538. doi: 10.1182/bloodadvances.2025016284.

  PMID: 40737543 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Tacrolimus; Sirolimus; Cyclophosphamide; In Vitro Techniques

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Investigative Techniques

Study Officials

• Jose-Antonio Perez-Simon, MD-PhD

  Hospitales Universitarios Virgen del Rocío

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: July 21, 2017
• Study Start: May 16, 2017
• Primary Completion: January 11, 2024
• Study Completion: December 31, 2024
• Last Updated: August 30, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 6 months after data completion
• Access Criteria: Investigators participating in the study until the final publication is done

Locations

ES (8)