AzTrials
AzTrials

Hematopoietic Stem Cell TransplantationPhase 1/2NCT03225417

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

A Phase 1/2 study testing Ixazomib, Tacrolimus and Sirolimus in people with Hematopoietic Stem Cell Transplantation and Multiple Myeloma, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 8 sites in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ixazomib, Tacrolimus and Sirolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
142 participants
Where
8 sitesSpain
Study dates
16 May 2017to 31 Dec 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 16Show fewer
  • 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.
  • Ability to understand the nature of this study and give written informed consent.

Who cannot join

  • 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.
Show all 17Show fewer
  • 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.
  • Active Graft versus host disease at the time of inclusion: patients are allowed to be included if acute Graft-versus-host Disease is in complete remission and are receiving systemic steroids at < 0.25 mg / kg.
  • Active hematologic malignancy at the time of inclusion.
  • Active microangiopathy at the time of inclusion (according to International Working Group criteria).
  • Gastrointestinal disease or procedure than can interfere with oral absorption , intolerance to the ixazomib or difficulty to swallow.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Spain8 sites

  • ICO- Hospital Germans Trias i Pujol

    Badalona

  • Hospital Clinic de Barcelona

    Barcelona

  • Hospital de la Santa Creu I Sant Pau

    Barcelona

  • Hospital Universitario Vall D´Hebrón

    Barcelona

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Clinico Universitario Salamanca

    Salamanca

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Hospital Clínico Universitario de Valencia

    Valencia

Other trials in Spain

About this study

Official title: Phase Ib/II Trial to Evaluate Safety and Efficacy of Oral Ixazomib in the Prophylaxis of Chronic Graft-versus-host Disease.

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.

Read the detailed description

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.

Being tested
Ixazomib, Tacrolimus, Sirolimus, Any prophylaxis for GVHD
Keywords
Ixazomib
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IxazomibDrug

    Also called X16082

    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.

  • TacrolimusDrug

    Also called Prograf

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

  • SirolimusDrug

    Also called Rapamune

    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.

  • Any prophylaxis for GVHDDrug

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

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

Study groups in NCT03225417
Study groupRoleWhat they receive
Experimental groupExperimentalPhase 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.
Receives: Drug: Ixazomib; Drug: Tacrolimus; Drug: Sirolimus; Drug: Any prophylaxis for GVHD
Control groupOtherAny prophylaxis for GVHD, except antithymocyte globulin, cyclophosphamide or any T depletion protocol in vitro or in vivo.
Receives: Drug: Tacrolimus; Drug: Sirolimus; Drug: Any prophylaxis for GVHD

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 3 months after transplantation (a total of 3 cycles of 28 days length of study treatment)

  2. 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.

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

Secondary outcomes (8)

  1. Event immune recovery for the phase I study

    Quantification of time of event immune recovery in patients exposed and not exposed to ixazomib.

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

  2. Event free survival for phase II study.

    Quantification of time of event free survival for patients receiving the maximum tolerated dose.

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

  3. Event immune recovery for phase II study.

    Quantification of time of event immune recovery in patients exposed and not exposed to ixazomib.

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

  4. Exposure to immunosuppressive treatment for phase II study.

    Evaluation of needs of additional permitted immunosuppressive treatment administered as concomitant medication

    Measured: 1 and 2 years after transplantation.

  5. Overall disease free survival for phase II study

    Quantification of time of overall survival after study treatment

    Measured: 2 years after transplantation.

  6. Serious adverse event for phase II study

    Describe the serious adverse event notified during the study

    Measured: 1 and 2 years after transplantation

  7. Risk of moderate or severe GVHD for phase II study

    To evaluate the risk of moderate or severe GVHD according to the NIH scale

    Measured: 2 years after transplantation

  8. 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

    Measured: 1 and 2 years after transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2017
  2. Study start16 May 2017
  3. Primary completion11 Jan 2024
  4. Study completion31 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
142 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03225417
Sponsor's protocol ID
X16082
Status last verified
Aug 2024
First submitted
4 Apr 2017
Last updated
30 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Anonymized data for primary and secondary variables is planned to be shared with all participants within 6 months of data completion.

Publications

  • 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.

    PubMed 40737543

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ixazomib, Tacrolimus and Sirolimus in people with Hematopoietic Stem Cell Transplantation and Multiple Myeloma, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 8 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 30 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximun tolerated dose (time frame: 3 months after transplantation (a total of 3 cycles of 28 days length of study treatment)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03225417, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in