Ixazomib in combination to thalidomide - dexamethasone for patients with relapsed and/or refractory multiple myeloma

Phase 1

• Conditions: refractory and/or relapsed multiple myeloma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-002749-23-DE
• Lead Sponsor: AGMT gGmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-06-22
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1.Male or female patients 18 years or older.
2.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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
3.Patients in need of therapy with a diagnosis of relapsed or refractory multiple myeloma who had at least one prior treatment line (induction + autologous SCT + consolidation + maintenance therapy = 1 therapy line)
4.Patients must have measurable disease defined by at least 1 of the following criteria:
•Serum M-protein = 10g/l
•Urine M-protein = 200mg/24h
•Serum free light chain assay: involved serum light chain = 10mg/dl provided that free light chain ration is abnormal
5.Life expectancy > 3 months
6.ECOG = 2
7.Patients must meet the following clinical laboratory criteria:
•Absolute neutrophil count (ANC) = 1.000/mm3 and platelet count = 50.000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
•Total bilirubin = 2 x ULN
•ALT and AST = 3 x ULN
•GFR = 15ml/min as calculated by Cockroft-Gault equation (see Appendix 13.2)
8.Female patients who:
•Are older than 50 years and postmenopausal for at least 1 year before the screening visit, OR
•Are surgically sterile, OR
•If they are of childbearing potential, agree to practice 2 effective methods of contraception at the same time, from 4 weeks before starting study therapy through 90 days after the last dose of study drug, OR
•Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
•Are informed and understand the possible consequences of the teratogenic potential of thalidomide
•All pregnancy prevention measurements for thalidomide described in the thalidomide prescribing information and thalidomide patient information leaflet need to be respected
9.Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
•Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
•Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
•Are informed and understand the possible consequences of the teratogenic potential of thalidomide
•All pregnancy prevention measurements for thalidomide described in the thalidomide prescribing information and thalidomide patient information leaflet need to be respected
10.Disease free of prior malignancies for = 2 years with exception of curatively treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ” of the cervix or breast if they have undergone complete resection.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1.Female patients who are lactating or have a positive serum pregnancy test during the screening period
2.Failure to have fully recovered (i.e., = Grade 1 toxicity) from the reversible effects of prior chemotherapy
3.Previous treatment with ixazomib
4.Previous treatment with bortezomib or thalidomide within the last 3 months prior to baseline visit (cycle 1/day 1)
5.Primary refractory to, or relapsing during, or within = 6 weeks after end of treatment with a proteasome inhibitor and/or thalidomide
6.Previous anti-cancer treatment within the last 21 days prior to baseline visit (cycle 1 / day 1), except corticosteroid therapy (40 - 160mg dexamethasone or corticosteroid dose equivalent per month)
7.Major surgery within 14 days before enrollment
8.Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib.
9.Central nervous system involvement
10.Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
11.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
12.Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort
13.Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
14.Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol
15.Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
16.Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
17.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 basal cell, squamous cell carcinoma of the skin, or carcinoma in situ” of the cervix or breast with are not excluded if they have undergone complete resection
18.Patient has = Grade 3 peripheral neuropathy or Grade 2 with pain on clinical examination during the screening period
19.Participation in other interventional 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified