Study Comparing Oral Ixazomib/Dexamethasone and Oral Pomalidomide/Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

Phase 1

Conditions: Relapsed and/or Refractory Multiple Myeloma
MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-004742-28-DE

Lead Sponsor: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

Adult patients (aged =18 years) who have been diagnosed with multiple myeloma (MM) according to standard criteria.
All patients must have had a relapse or PD after having received 2 or more prior lines of systemic therapy. (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 stem-cell transplantation, followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD.)
All patients 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.
All patients must have received at least 2 consecutive cycles of a bortezomib- or carfilzomib-containing regimen, and either:
– Achieved at least a partial response (PR) and did not have PD during treatment with or within 60 days after the last dose of bortezomib or carfilzomib, OR
– 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 upon the start of the next regimen.
All patients must have an Eastern Cooperative Oncology Group score of 0 to 2.
All patients 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).
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 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be
enrolled in the study:
1. Patients must not have received prior ixazomib or pomalidomide and must not have been a participant in a previous ixazomib clinical study.
2. 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.
3. Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
4. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol, such as life-threatening illness unrelated to cancer.
5. 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.
Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
6. Diagnosis of smoldering MM (see Appendix D), Waldenström's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, oclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
7. Known allergy to any of the study medications or their analogues, or excipients in the various formulations.
8. Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the
Screening period.
9. 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.
10. Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of study therapy, including difficulty swallowing.
11. Serious infection requiring parenteral antibiotic therapy or any other serious infection within 14 days before randomization.
12. Central nervous system involvement with MM (by clinical symptoms and signs).
13. Ongoing or active systemic infection, known human immunodeficiency virus-RNA positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive. Note: Patients who have positive hepatitis B core antibody can be enrolled but must have hepatitis B virus-DNA negative. Patients who have positive hepatitis C antibody can be enrolled but must have hepatitis C virus-RNA negative.
14. 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.
15. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
16. History of severe cutaneous reactions, including hypersensitivity reactions such as Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), in the context of treatment with lenalidomide, or thalidomide (see Section 8.7 for more information).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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