A Phase 2, Randomized, Open-Label Study Comparing Oral Ixazomib/Dexamethasone and Oral Pomalidomide/Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

Phase 2

Completed

• Conditions: Kahler's disease; Multiple Myeloma (MM); 10035227

• Registration Number: NL-OMON48607
• Lead Sponsor: Millenium Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2022-07-18
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 12

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).

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be enrolled
in the study:
- Patients must not have received prior ixazomib or pomalidomide and must not
have been a participant in a previous ixazomib clinical study.
- 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.
- Female patients who are lactating and breastfeeding or have a positive serum
pregnancy test during the Screening period.
- 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.
- 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.
- Diagnosis of smoldering MM (see Appendix D), Waldenström's macroglobulinemia,
POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and
skin changes) syndrome, plasma cell leukemia, primary amyloidosis,
myelodysplastic syndrome, or myeloproliferative syndrome.
- Known allergy to any of the study medications or their analogues, or
excipients in the various formulations.
- 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-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.
- 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.
- 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 <br

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Progression-free survival (PFS), defined as the time from randomization to the<br /><br>first occurrence of confirmed progressive disease (PD), as evaluated by the<br /><br>investigator, according to International Myeloma Working Group (IMWG) criteria,<br /><br>or death from any cause, whichever occurs first.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary endpoints are OS, measured as the time from randomization to<br /><br>death from any cause; ORR (defined as complete response, very good partial<br /><br>response (VGPR), or PR [per IMWG criteria]); duration of response; time to<br /><br>response; time to progression (TTP); health-related QOL as measured by the<br /><br>physical domain of the EORTC QLQ-C30; health-related QOL as measured by other<br /><br>domains of the EORTC QLQ-C30, by the EORTC QLQ-MY20, and by the EQ-5D-5L;<br /><br>health care utilization as measured by the number and duration of medical<br /><br>encounters; and safety/tolerability.<br /><br>After the primary endpoint of PFS has been met, all central efficacy and<br /><br>investigator assessments of response for protocol purposes will be<br /><br>discontinued; patients will be followed for survival and the appropriate data<br /><br>collected.</p><br>