A Study of Ixazomib Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
A Study of Ixazomib Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
The purpose of Phase 1 of this study was to determine the safety, tolerability, maximum
 tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of oral ixazomib administered in
 combination with lenalidomide and low-dose dexamethasone in participants with newly diagnosed
 multiple myeloma (NDMM). The purpose of Phase 2 of this study was to determine the overall
 response rate (ORR) and further evaluate the tolerability and toxicity of the combination of
 oral ixazomib, lenalidomide, and low-dose dexamethasone in patients with NDMM.
The drug being tested in this study is called ixazomib. Ixazomib was being tested to treat
 people who had newly diagnosed multiple myeloma who had not previously received systemic
 treatment. This study was conducted in two Phases. Phase 1 looked at side effects and lab
 results in people who took ixazomib to determine the MTD and RP2D. Phase 2 looked at overall
 response rates and side effects in people who took ixazomib.

 The study enrolled 15 patients in Phase 1 and 50 patients in Phase 2. Participants in Phase 1
 were assigned to cohorts and received ixazomib 1.68, 2.23, 2.97, or 3.95 mg/m^2 in addition
 to dexamethasone 40 mg and lenalidomide 25 mg. Participants in Phase 2 received ixazomib 4.0
 mg fixed dose in addition to dexamethasone 40 mg and lenalidomide 25 mg. In both Phases study
 treatment was administered in 28-day Cycles as follows: ixazomib Days 1, 8 and 15,
 dexamethasone Days 1, 8, 15 and 22, and lenalidomide 25 mg Days 1 through 21.

 This multi-center trial was conducted in the United States. The overall time to participate
 in this study was 12, 28-day cycles with the option to continue into a maintenance portion in
 the absence of disease progression or unacceptable toxicity. Participants made multiple
 visits to the clinic and a final visit 30 days after last dose of study drug for a follow-up
 assessment.
Inclusion Criteria:

 Each patient must meet all of the following eligibility criteria to be enrolled in the
 study:

 -  Male or female patients 18 years or older

 -  Previously untreated multiple myeloma diagnosed according to standard criteria
 requiring systemic treatment

 -  Patients must have measurable disease

 -  Nonsecretory multiple myeloma based upon standard M-component criteria (i.e.,
 measurable serum/urine M-component) is not allowed unless the baseline serum free
 light chain level (Freelite™) is evaluated Patients must meet clinical laboratory
 criteria as specified in study protocol

 -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

 -  Female and male patients MUST adhere to the guidelines of the lenalidomide pregnancy
 prevention program

 -  Must be able to take concurrent aspirin 325 mg daily

 -  Voluntary written consent

 Exclusion Criteria

 Patients meeting any of the following exclusion criteria are not to be enrolled in the
 study:

 -  Peripheral neuropathy that is greater or equal to Grade 2

 -  Female patients who are lactating or pregnant

 -  Major surgery or radiotherapy within 14 days before the first dose of study drug

 -  Serious infection requiring systemic antibiotic therapy within 14 days before the
 first dose of study drug

 -  Diarrhea greater than Grade 1 based on the National Cancer Institute Common
 Terminology Criteria for Adverse Events

 -  Central nervous system involvement.

 -  Evidence of current uncontrolled cardiovascular conditions within the past 6 months

 -  Known human immunodeficiency virus (HIV) positive, hepatitis B surface
 antigen-positive status, or known or suspected active hepatitis C infection

 -  Serious medical or psychiatric illness that could, in the investigator's opinion,
 potentially interfere with the completion of treatment according to the protocol

 -  Known gastrointestinal condition that could interfere with swallowing or the oral
 absorption or tolerance of ixazomib

 -  No other prior malignancy within 2 years except nonmelanoma skin cancer or carcinoma
 in situ of any type if they have undergone complete resection