An Efficacy Study Comparing Oral Ixazomib / Dexamethasone and Oral Pomalidomide / Dexamethasone in Relapsed and / or Refractory Multiple Myeloma
The purpose of this study is to compare the effect of ixazomib + dexamethasone (ixa + dex) versus pomalidomide + dexamethasone (pom + dex) on progression-free survival (PFS) in participants with relapsed and / or refractory multiple myeloma (RRMM) who have received at least 2 prior lines of therapy, including lenalidomide and a proteasome inhibitor, and are refractory to lenalidomide but not refractory to proteasome inhibitors.
- Must have a confirmed diagnosis of multiple myeloma (MM) requiring therapy according to IMWG criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Must have had a relapse or PD after having received 2 or more prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more cycles of a planned treatment program; this may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous SCT, followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD. Discussion with the medical monitor may help clarify the number of lines of therapy that a prospective study participant had.
- Must be refractory to lenalidomide, defined as having received at least 2 consecutive cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen and having had PD during treatment with or within 60 days after the last dose of lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as 10 mg in the case of renal function impairment or other safety concern), and the final dose should have been a minimum of 10 mg.
- Must have received at least 2 consecutive cycles of a bortezomib- or carfilzomib-containing regimen, and either: Achieved at least a PR and did not have PD during treatment with or within 60 days after the last dose of bortezomib or carfilzomib, OR o Had bortezomib and/or carfilzomib intolerance (defined as discontinuation because of drug-related adverse events [AEs] before completion of the planned treatment course) without PD before the start of the next regimen.
- Must have measurable disease defined by:
- Serum M-protein >=1 g/dL (>=10 g/L), OR
- Urine M-protein >=200 mg/24 hours and must have documented MM isotype by immunofixation (central laboratory).
- Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling.
- Recovered (that is, less than or equal to [<=] Grade 1 nonhematologic toxicity) from the reversible effects of prior anticancer therapy.
- Must be willing and able to adhere to pomalidomide-related risk mitigation activities if randomized to the pom+dex arm (example, Risk Evaluation and Mitigation Strategies [REMS], pregnancy prevention programs).
- Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy- unless the autologous SCT was performed a year or more before disease progression.
- Diagnosed with or treated for another malignancy within 2 years before randomization, or previously diagnosed with another malignancy and have any evidence of residual, persistent, or recurrent disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
- Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period.
- Treatment with any investigational products or with chimeric or fully human monoclonal antibodies within 30 days before randomization, systemic anticancer therapy or radiotherapy within 14 days before randomization (Note: "spot" radiation for areas of pain is permitted), and major surgery within 14 days before randomization.
- Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of study therapy, including difficulty swallowing.
- Serious infection requiring parenteral antibiotic therapy or any other serious infection within 14 days before randomization.
- Central nervous system involvement with MM (by clinical symptoms and signs).
- Ongoing or active systemic infection, known human immunodeficiency virus-ribonucleic acid (RNA) positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive.
- Systemic treatment with strong cytochrome P-450 3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before randomization.
- Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
Locations & Contacts
Contact: Zahid Noor
Name Not Available
Trial Objectives and Outline
The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have RRMM. This study will compare the efficacy and safety in participants who take ixazomib and dexamethasone to pomalidomide and dexamethasone. It is an open-label, phase 2 study that, on the basis of a prespecified go/no-go decision rule, will progress to a phase 3 registrational study. The study will enroll approximately 300 patients. Participants will receive: - Ixazomib 4 mg + dexamethasone 20 mg (or 10 mg if participant is aged >=75 years) OR - pomalidomide 4 mg + dexamethasone 40 mg (or 20 mg if participant is aged >=75 years) All participants will be asked to take either ixazomib plus dexamethasone (in cases where only 4 mg tablets for dexamethasone are available, the following dexamethasone schedule is recommended for participants aged >=75 years: 12 mg dexamethasone will be given on Days 1, 8, 15, and 22 of every 28-day cycle; and 8 mg dexamethasone will be given on Days 2, 9, 16, and 23 of every 28-day cycle) or pomalidomide 4 mg + dexamethasone 40 mg at recommended doses. This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 63 months if the phase 3 portion of the study is completed. Alternatively, if the no-go criteria are met during the phase 2 portion, the study will be completed approximately 22 to 29 months after the first participant enters the study. Participants will make multiple visits to the clinic, and will be contacted for PFS follow-up, in case of study drug discontinuation for up to 7 years from first dose administration. After disease progression, participants will be followed-up for OS every 12 weeks until death or up to 10 years.
Trial Phase & Type
Millennium Pharmaceuticals, Inc.
Secondary IDs NCI-2018-00875, 2016-004742-28, 17/NW/0546, N-20170083, 2017/1235, U1111-1188-2677
Clinicaltrials.gov ID NCT03170882