Relapsed/refractory multiple myeloma MedDRA version: 21.1 Level: LLT Classification code 10067095 Term: Multiple myeloma progression System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Imnovid
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pomalidomide
CAS Number: 19171-19-8
Current Sponsor code: Pomalidomide
Other descriptive name: POMALIDOMIDE
Concentration un
Sponsors
GWT-TUD GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female patients = 18 years of age at the time of signing the informed consent form • Patients capable to understand the purposes and risks of the study, who are willing and able to participate in the study and from whom written and dated informed consent to participate in the study has been obtained prior to any study related assessments/ procedures being conducted- In the event that patients lose the capacity to consent, they must be withdrawn from the study immediately- • Patients with relapsed or refractory, histologically confirmed multiple myeloma • Patients must have had at least 2 but no greater than 4 prior antimyeloma regimens, including lenalidomide and bortezomib. (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered 1 regimen.) • Patients must have had documented disease progression during or after their last antimyeloma therapy • Patients must have received prior treatment with a LEN-containing regimen for at least 2 consecutive cycles • Measurable levels of serum and/or urine M-protein: serum M-protein = 5 g/L and/or urine M-protein = 200 mg/24h or serum free light chain (sFLC) concentration of > 100 mg/L of the involved FLC, provided sFLC ratio is abnormal (sFLC K/? ratio ( 1.65) • Life expectancy = 3 months • ECOG performance status of 0, 1, or 2 • Patients must be able to adhere to the study visit schedule and other protocol requirements • All women and men must acknowledge to have understood the hazards and necessary precautions associated with the use of pomalidomide and ixazomib • All subjects must agree in writing to strictly adhere to the Pomalidomide Pregnancy Prevention Plan as given in Appendix C • Females of childbearing potential (FCBP) must: o Understand the potential teratogenic risk to the unborn child o Agree to utilize two reliable forms of contraception simultaneously without interruption for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 90 days after study treatment discontinuation o Be capable of complying with effective contraceptive measures o Be informed and understand the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy o Understand the need to commence the study treatment as soon as study drug is dispensed following a negative pregnancy test o Understand the need and accept to undergo pregnancy testing based on the frequency outlined in this protocol • Females must agree to abstain from breastfeeding during study participation and for at least 28 days after study drug discontinuation • Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 90 days following discontinuation from this study, even if he has undergone a successful vasectomy • Males must also agree to refrain from donating semen or sperm while on the study drugs and for 90 days after discontinuation from this study treatment • Subjects must agree to refrain from donating blood while on study therapy and for 28 days after discontinuation from this study treatment • Subjects must agree not to share medication • Patients must meet the following clinical laboratory criteria: o Absolute neutrophil count (ANC) ? 1 x 109/L o Platelet count ? 75 x 109/L for patients in whom < 50% of bone marrow nucleated cells are plasma cells o Platelet count = 30 x
Exclusion criteria
Exclusion criteria: • Concomitant cancer chemo- or radiotherapy (except for local radiation therapy for preexisting lytic lesions) • Treatment with any investigational product within 60 days prior to first administration of pomalidomide and ixazomib • Patients eligible for autologous and / or allogeneic stem cell transplantation • Abnormal/inadequate organ or bone marrow function as defined below (any single parameter to fulfill condition): o ANC 3 x upper limit of normal (ULN) o Serum (total) bilirubin > 1.5 x ULN o Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L); or free ionized calcium > 6.5 mg/dL (> 1.6 mmol/L) • Prior pomalidomide based therapy • Prior ixazomib based therapy • Baseline peripheral neuropathy > Grade 1 on clinical examination within 14 days before enrollment • Active HIV, hepatitis B (including patients who are tested Anti-HBc-positive and / or HBsAg-positive) or hepatitis C infection after serologic testing • Any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the study as judged by the investigator • Known hypersensitivity to pomalidomide and its analogues in general and/or to ixazomib and its analogues or to any other component of study drugs • Prior malignancy excluding adequately treated with curative intent basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer without any evidence of residual disease or requiring anti-cancer treatment < 2 years prior to initiating study treatment • Patients with congestive heart failure NYHA Class III and IV, cardiac arrhythmias (except atrioventricular block type I and II, atrial fibrillation/flutter, bundle brunch block) or other signs and symptoms of relevant cardiovascular disease • Pregnant women, nursing mothers, lactating women, and women of childbearing potential as well as male subjects who are unwilling to adhere to the guidelines of the treatment-specific pregnancy prevention program • Unwilling or unable to follow protocol requirements • Systemic treatment 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 within 14 days before randomization in the study • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of the study drugs including difficulty swallowing • Inability or unwillingness to receive thromboembolism prophylaxis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the clinical activity of pomalidomide administered once daily in combination with oral ixazomib and dexamethasone (PId);Secondary Objective: To assess the safety and feasibility of PId and the efficacy, safety and feasibility of PId intensified by low-dose cyclophosphamide (PICd);Primary end point(s): The primary endpoint is the overall response rate to PId, according to the IMWG criteria (i.e., partial response and better).;Timepoint(s) of evaluation of this end point: Time to response is calculated as the time from study enrollment to the first documented response (PR or better) based on IMWG criteria. Response assessments will be performed every four weeks by evaluation of serum and 24 hour urine specimens. “Progressive disease” (PD) will require a consecutive confirmatory measurement. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Disease control rate in patients receiving PId (at least SD) •Overall response rate (PR or better) for patients intensified with PICd •Disease control rate in patients intensified with PICd (at least SD) •Progression-free survival (PFS) for patients receiving PId •PFS for patients receiving PICd •Overall survival (OS) •To evaluate the safety of the dosing regimens applied in this study (incidence, severity and relationship of AEs/SAEs) •To evaluate best response during induction by PId •To assess molecular cytogenetic abnormalities ;Timepoint(s) of evaluation of this end point: Duration of response, calculated for responders only, is defined as time from the initial documented response (PR or better) to the first confirmed PD. Time to progression will be calculated as the time from study enrollment until PD (as determined by the site investigator based on the IMWG criteria). Progression-free survival will be calculated as the time from study enrollment until the time of PD (as determined by the site investigator based on the IMWG criteria) or death from any cause on study treatment. Overall survival will be calculated as the time from study enrollment until the time of death from any cause. If no death is recorded the subject will be censored at the time the subject was last known to be alive. | — |
Countries
Germany
Contacts
Public ContactGWT-TUD GmbH
GWT-TUD GmbH
Outcome results
None listed