Efficacy and Safety of Ixazomib and Dexamethasone Refractory Autoimmune Cytopenia

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03965624
• Date of registration: 24/05/2019
• Prospective Registration: Yes
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Efficacy and Safety of Ixazomib and Dexamethasone Refractory Autoimmune Cytopenia Ixa-Cyto
• Scientific title: A Prospective Open-label Trial to Assess the Efficacy and Safety of Ixazomib and Dexamethasone in Patients With Refractory Autoimmune Cytopenia
• Date of first enrolment: September 1, 2019
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03965624
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Matthieu Mahevas
• Affiliation: Assistance Publique - Hôpitaux de Paris

Key inclusion & exclusion criteria

Inclusion Criteria:

ITP patients:

1. Age >= 18 years

2. Diagnosis of ITP according to the international definition (Rodeghiero et al Blood
2009)

3. 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.

4. 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

1. Age >= 18 years

2. Diagnosis of wAIHA , symptomatic anemia and a positive direct antiglobulin test

3. 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;

1. Absolute neutrophil count (ANC) >=1,000/mm3

2. Gammablobulin level > 7 g/l

3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3x ULN.

4. Calculated creatinine clearance >=30 mL/min

5. 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be withdrawn by the patient at any time without prejudice to future medical care.

Exclusion criteria

1. Major surgery within 14 days before enrollment.

2. Infection requiring systemic antibiotic therapy or other serious infection within 14
days before study enrollment.

3. Female patients who are lactating or have a positive serum pregnancy test during the
screening period.

4. 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.

5. 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.

6. ) 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.

7. Any serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the completion of treatment according to this protocol.

8. Known allergy to any of the study medications, their analogues, or excipients in the
various formulations of any agent.

9. Known GI disease or GI procedure that could interfere with the oral absorption or
tolerance of ixazomib including difficulty swallowing.

10. 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.

11. Unable to comply with study and follow-up procedures due to psychiatric disorders or
any other reason.

12. Inflammatory central nervous system disorder.

13. Patient has >=Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical
examination during the screening period.

14. 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.

15. Patients that have previously been treated with ixazomib, or participated in a study
with ixazomib whether treated with ixazomib or not.

16. Total bilirubin = 1.5 x the upper limit of the normal range (ULN).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Warm Autoimmune Hemolytic Anemia

Immune Thrombocytopenia

Intervention(s)

Drug: Ninlaro

Primary Outcome(s)

Rate of patients achieving a response (CR+R) with 5 cycles without severe toxicity (grade III/IV) [Time Frame: 6 months]

Secondary Outcome(s)

Anti-platelets/red blood cells antibodies (Ancillary study) [Time Frame: Day 0, Day 84, 6 months]

Number and program of bone marrow pathogenic plasma cells for patients with refractory disease (Ancillary study). [Time Frame: Day 0, 6 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.]

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.]

Gammablobulin level (and isotype) along the study [Time Frame: Day 28, Day 56, Day 84, Day 112, 9 months and 12 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]

Number of pathogenic circulating plasmablasts (Ancillary study) [Time Frame: Day 0, 28, 56, 84, 112 months 6, 9, 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]

Protective antibody titers (measles, mumps, tetanus) (Ancillary Study) [Time Frame: Day 0, Day 84, 6 months, 9 months and 12 months]

Secondary ID(s)

P171201J

2018-004556-38

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Takeda Pharmaceuticals International, Inc.