Immune ThrombocytopeniaPhase 2Ixa-CytoNCT03965624
Efficacy and Safety of Ixazomib and Dexamethasone Refractory Autoimmune Cytopenia
A Phase 2 study testing Ninlaro in people with Immune Thrombocytopenia and Warm Autoimmune Hemolytic Anemia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Some patients with antibody-mediated autoimmune hematological diseases (warm autoimmune hemolytic anemia (wAIHA), cold agglutinin disease (cAIHA) and immune thrombocytopenia (ITP)) shows no or only minor and transient response to therapy despite several treatment-lines. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immune Thrombocytopenia, Warm Autoimmune Hemolytic Anemia
- What is being tested?
- Ninlaro
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- 1 Sep 2019to 1 Sep 2023
- Phase
- Phase 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
- ITP patients:
- Age >= 18 years
- Diagnosis of ITP according to the international definition (Rodeghiero et al Blood 2009)
- Platelets count < 30 x 109/L or <50 x 109/L if presence of hemorrhagic events or other reason left up to investigator discretion within the months preceding inclusion.
- Multirefractory ITP defined as patients who have previously failed to maintain a response after rituximab (anti-CD20), splenectomy, and romiplostim and eltrombopag, except if patients have any contraindications or refused these treatments
- wAIHA patients
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- Age >= 18 years
- Diagnosis of wAIHA , symptomatic anemia and a positive direct antiglobulin test
- Refractory AIHA who have previously failed to maintain a sustained response after rituximab (anti-CD20) and splenectomy except if patients have any contraindications or refused these treatments.
- For all patients;
- Absolute neutrophil count (ANC) >=1,000/mm3
- Gammablobulin level > 7 g/l
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3x ULN.
- Calculated creatinine clearance >=30 mL/min
- Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
Who cannot join
- Major surgery within 14 days before enrollment.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
- Female patients who are lactating or have a positive serum pregnancy test during the screening period.
- 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 CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, azathioprine), or use of St. John's wort.
- ) Positive HIV test and/or hepatitis virus C infection and/or positive hepatitis B virus surface antigen or core antibody (HbsAg or HBcAb) and/or Active Varicella or Herpes and zoster infection.
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- 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.
- Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
- 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.
- Unable to comply with study and follow-up procedures due to psychiatric disorders or any other reason.
- Inflammatory central nervous system disorder.
- Patient has >=Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.
- 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.
- Total bilirubin ≥ 1.5 x the upper limit of the normal range (ULN).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Open-label Trial to Assess the Efficacy and Safety of Ixazomib and Dexamethasone in Patients With Refractory Autoimmune Cytopenia
Some patients with antibody-mediated autoimmune hematological diseases (warm autoimmune hemolytic anemia (wAIHA), cold agglutinin disease (cAIHA) and immune thrombocytopenia (ITP)) shows no or only minor and transient response to therapy despite several treatment-lines. Such patients are more likely to have a severe disease, with a higher morbidity and mortality.
Hypothesis Effective depletion of autoreactive plasma cells might be the key for a curative approach of these diseases. Therefore, there is a rationale for using proteasome inhibitors (PIs) in these refractory patients.
Read more
The rationale is that non-tumoral autoreactive plasma cells are rapidly targeted by proteasome inhibitors. It led us to propose a short course of dexamethasone and ixazomib (5 cycles), to evaluate the safety/efficacy of this innovative strategy of treatment.
Method Prospective interventional uncontrolled single arm open study evaluating the rate of patients achieving 5 cycles of ixazomib and dexamethasone without severe toxicity and response on therapy.
- Being tested
- Ninlaro
- Keywords
- MCNS, Rituximab, Complete remission
- Medical subject headings
- Purpura, Thrombocytopenic, Idiopathic, Pathologic Complete Response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NinlaroDrug
Also called Ixazomib
Oral ixazomib will be given on days 1, 8, 15 of a 28-day cycle, the investigator will start with first test dose levels of ixazomib of 3 mg and process with dose escalation, in case of non-response and no severe adverse events at cycle 1 (see above) or de-escalation in case of response and severe adverse events.
| Study group | Role | What they receive |
|---|---|---|
| Ixazomib | Experimental | Oral ixazomib will be given on days 1, 8, 15 of a 28-day cycle, in combination with dexamethasone 20 mg weekly. The investigator will start with first test dose levels of ixazomib of 3 mg and process with dose escalation, in case of non-response and no severe adverse events at cycle 1 (see below) or de-escalation in case of response and severe adverse events. Receives: Drug: Ninlaro |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of patients achieving a response (CR+R) with 5 cycles without severe toxicity (grade III/IV)
Criteria of response:
ITP: A complete response is defined by a platelet count > 100 x 109/L maintained in the absence of any other ITP directed therapies. A responder to treatment is defined by a patient with a maintained platelet count at > 30 x109/L (Rodeghiero et al Blood 2008) and a minimum twofold increase from initial platelet levels in the absence of bleeding and/or use of ITP directed therapies.
AIHA: Complete response (CR) is defined as normalization in haemoglobin concentration (Hb≥12 g/dL) without any ongoing immunosuppressive treatment and without any biochemical signs of hemolytic activity. Response (R) is defined as a haemoglobin concentration ≥10 g/dL and requiring continued low-dose prednisolone (<20 mg/day prednisone) or at least 2 g/dL increase in Hb, and no transfusion requirement
Measured: 6 months
Secondary outcomes (10)
Number of patients responding to treatment (CR+R)
CR=complete response, R= Response
Measured: At Day 28, Day 56, Day 84, Day 112, 6 months, 9 months and 12 months.
Number of patients experiencing a A treatment-emergent adverse event (TEAE) along the course of the study.
A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug (AE start date ≥ first dose date) and within 30 days after receiving the last dose of study drug. TEAE will be scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 4. A severe toxicity severe toxicity is defined as ≥ grade III.
For ITP patients, thrombocytopenia will not be included in TEAE if it is due to disease activity. But severe bleeding manifestations as unexpected severe hemorrhagic events defined as intracranial hemorrhage, gastrointestinal or visceral bleeding with a decrease of hemoglobin by more than 2 g/dl should be reported as SAE.
For AIHA patients, anemia will not be included in TEAE if it is due to disease activity. But, severe, unexpected anemia (less thant 6 g/dl) in patients who have previously achieved a response should be reported as SAE.
Measured: Up to 12 months
Gammablobulin level (and isotype) along the study
Measured: Day 28, Day 56, Day 84, Day 112, 9 months and 12 months
Number of infectious events along the study
Measured: Up to 12 months
Number of bleeding manifestations according to the French bleeding score for ITP patients
Measured: At Day 28, Day 56, Day 84, Day 112, 6 months, 9 months and 12 months.
Protective antibody titers (measles, mumps, tetanus) (Ancillary Study)
Measured: Day 0, Day 84, 6 months, 9 months and 12 months
Number of pathogenic circulating plasmablasts (Ancillary study)
Measured: Day 0, 28, 56, 84, 112 months 6, 9, 12 months
Number and program of bone marrow pathogenic plasma cells for patients with refractory disease (Ancillary study).
Measured: Day 0, 6 months
Anti-platelets/red blood cells antibodies (Ancillary study)
Measured: Day 0, Day 84, 6 months
Level of serum cytokines (Ancillary study)
Measured: Day 0, Day 28, Day 56, Day 84, Day 112 and 6 months , 9 months , 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2019
- Study start1 Sep 2019 (estimated)
- Primary completion1 Mar 2023 (estimated)
- Study completion1 Sep 2023 (estimated)
Why it stopped: Decision of sponsor: impossibility of contract with Takeda
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immune ThrombocytopeniaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective interventional uncontrolled single arm open study evaluating the rate of patients achieving 5 cycles without severe toxicity and response on therapy: Interventional clinical study phase IIb , Non-comparative, Not randomised, Not controlled, Unblinded. Oral ixazomib will be given on days 1, 8, 15 of a 28-days cycle, in combination with dexamethasone 20 mg weekly. The investigator will start with first test dose levels of ixazomib of 3 mg and process with dose escalation, in case of non-response and no severe adverse events at cycle 1 or de-escalation in case of response and severe adverse events.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda Pharmaceuticals International, Inc.
- Responsible party
- Sponsor
- Investigators
- Matthieu Mahevas, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03965624
- Sponsor's protocol ID
- P171201J
- Other IDs
- 2018-004556-38, 2018
- Acronym
- Ixa-Cyto
- Status last verified
- Dec 2018
- First submitted
- 24 May 2019
- Last updated
- 28 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Open-label Trial to Assess the Efficacy and Safety of Ixazomib and Dexamethasone in Patients With Refractory Autoimmune Cytopenia
- ClinicalTrials.gov ID
- NCT03965624
- Acronym / sponsor ID
- Ixa-Cyto / P171201J
- Keywords
- MCNS, Rituximab, Complete remission
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Decision of sponsor: impossibility of contract with Takeda
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Takeda Pharmaceuticals International, Inc.
- Study start
- 1 Sep 2019 (estimated)
- Primary completion
- 1 Mar 2023 (estimated)
- Study completion
- 1 Sep 2023 (estimated)
- First posted
- 29 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Some patients with antibody-mediated autoimmune hematological diseases (warm autoimmune hemolytic anemia (wAIHA), cold agglutinin disease (cAIHA) and immune thrombocytopenia (ITP)) shows no or only minor and transient response to therapy despite several treatment-lines. Such patients are more likely to have a severe disease, with a higher morbidity and mortality.
Hypothesis Effective depletion of autoreactive plasma cells might be the key for a curative approach of these diseases. Therefore, there is a rationale for using proteasome inhibitors (PIs) in these refractory patients.
The rationale is that non-tumoral autoreactive plasma cells are rapidly targeted by proteasome inhibitors. It led us to propose a short course of dexamethasone and ixazomib (5 cycles), to evaluate the safety/efficacy of this innovative strategy of treatment.
Method Prospective interventional uncontrolled single arm open study evaluating the rate of patients achieving 5 cycles of ixazomib and dexamethasone without severe toxicity and response on therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective interventional uncontrolled single arm open study evaluating the rate of patients achieving 5 cycles without severe toxicity and response on therapy: Interventional clinical study phase IIb , Non-comparative, Not randomised, Not controlled, Unblinded. Oral ixazomib will be given on days 1, 8, 15 of a 28-days cycle, in combination with dexamethasone 20 mg weekly. The investigator will start with first test dose levels of ixazomib of 3 mg and process with dose escalation, in case of non-response and no severe adverse events at cycle 1 or de-escalation in case of response and severe adverse events.
| Arm | Type | Receives |
|---|---|---|
| Ixazomib | Experimental | Drug: NinlaroOral ixazomib will be given on days 1, 8, 15 of a 28-day cycle, in combination with dexamethasone 20 mg weekly. The investigator will start with first test dose levels of ixazomib of 3 mg and process with dose escalation, in case of non-response and no severe adverse events at cycle 1 (see below) or de-escalation in case of response and severe adverse events. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age >= 18 years
- Diagnosis of ITP according to the international definition (Rodeghiero et al Blood 2009)
- Platelets count < 30 x 109/L or <50 x 109/L if presence of hemorrhagic events or other reason left up to investigator discretion within the months preceding inclusion.
- Multirefractory ITP defined as patients who have previously failed to maintain a response after rituximab (anti-CD20), splenectomy, and romiplostim and eltrombopag, except if patients have any contraindications or refused these treatments
- wAIHA patients
Key exclusion criteria (16 listed)
- Major surgery within 14 days before enrollment.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
- Female patients who are lactating or have a positive serum pregnancy test during the screening period.
- 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 CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, azathioprine), or use of St. John's wort.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NinlaroAlso: IxazomibOral ixazomib will be given on days 1, 8, 15 of a 28-day cycle, the investigator will start with first test dose levels of ixazomib of 3 mg and process with dose escalation, in case of non-response and no severe adverse events at cycle 1 (see above) or de-escalation in case of response and severe adverse events. | Drug | Ixazomib |
Primary outcome
Rate of patients achieving a response (CR+R) with 5 cycles without severe toxicity (grade III/IV)
Time frame: 6 months
Criteria of response: ITP: A complete response is defined by a platelet count > 100 x 109/L maintained in the absence of any other ITP directed therapies. A responder to treatment is defined by a patient with a maintained platelet count at > 30 x109/L (Rodeghiero et al Blood 2008) and a minimum twofold increase from initial platelet levels in the absence of bleeding and/or use of ITP directed therapies. AIHA: Complete response (CR) is defined as normalization in haemoglobin concentration (Hb≥12 g/dL) without any ongoing immunosuppressive treatment and without any biochemical signs of hemolytic activity. Response (R) is defined as a haemoglobin concentration ≥10 g/dL and requiring continued low-dose prednisolone (<20 mg/day prednisone) or at least 2 g/dL increase in Hb, and no transfusion requirement
10 secondary outcomes
Number of patients responding to treatment (CR+R)
Time frame: At Day 28, Day 56, Day 84, Day 112, 6 months, 9 months and 12 months.
Number of patients experiencing a A treatment-emergent adverse event (TEAE) along the course of the study.
Time frame: Up to 12 months
Gammablobulin level (and isotype) along the study
Time frame: Day 28, Day 56, Day 84, Day 112, 9 months and 12 months
Number of infectious events along the study
Time frame: Up to 12 months
Number of bleeding manifestations according to the French bleeding score for ITP patients
Time frame: At Day 28, Day 56, Day 84, Day 112, 6 months, 9 months and 12 months.
Protective antibody titers (measles, mumps, tetanus) (Ancillary Study)
Time frame: Day 0, Day 84, 6 months, 9 months and 12 months
Number of pathogenic circulating plasmablasts (Ancillary study)
Time frame: Day 0, 28, 56, 84, 112 months 6, 9, 12 months
Number and program of bone marrow pathogenic plasma cells for patients with refractory disease (Ancillary study).
Time frame: Day 0, 6 months
Anti-platelets/red blood cells antibodies (Ancillary study)
Time frame: Day 0, Day 84, 6 months
Level of serum cytokines (Ancillary study)
Time frame: Day 0, Day 28, Day 56, Day 84, Day 112 and 6 months , 9 months , 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2019.
- Individual participant dataSharing planned: No. DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthieu Mahevas principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ninlaro in people with Immune Thrombocytopenia and Warm Autoimmune Hemolytic Anemia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 15 inclusion and 16 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: withdrawn, as of the sponsor's last update on 28 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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 phase mean?
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Rate of patients achieving a response (CR+R) with 5 cycles without severe toxicity (grade III/IV) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Oct 2019.