IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma

Millennium Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Lenalidomide; Drug: Ixazomib; Drug: Dexamethasone; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01850524

163325 (Registry Identifier)

U1111-1158-2646 (Registry Identifier)

C16014

2013-000326-54 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to provide continued access to ixazomib and/or lenalidomide to participants who are continuing to have clinical benefit and to continue collecting relevant safety data to monitor safety in participants with Newly Diagnosed Multiple Myeloma (NDMM) who are not eligible for stem cell transplant.

Enrollment: 705 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female participants 18 years or older diagnosed with Multiple Myeloma according to standard criteria who have not received prior treatment for multiple myeloma.

2. Participants for whom lenalidomide and dexamethasone treatment is appropriate and who are not eligible for high-dose therapy followed by stem-cell transplantation (HDT-SCT) for 1 or more of the following reasons:

   • The participant is 65 years of age or older.
   • The participant is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT.

3. Measurable disease as specified in study protocol.

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

5. Meet the clinical laboratories criteria as specified in the protocol.

6. Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence, and must also agree to ongoing pregnancy testing; must also adhere to the guidelines of the lenalidomide pregnancy prevention program.

7. Male participants who agree to practice effective barrier contraception or agree to practice true abstinence AND must adhere to the guidelines of the lenalidomide pregnancy prevention program.

8. Suitable venous access for the study-required blood sampling.

9. Must be able to take concurrent aspirin 70 mg to 325 mg daily (or enoxaparin if aspirin allergic).

10. Voluntary written consent.

11. Participant is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion criteria

1. Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen.
2. Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
3. Inability or unwillingness to receive antithrombotic therapy.
4. Female participants who are lactating or pregnant.
5. Major surgery or radiotherapy within 14 days before randomization.
6. Infection requiring intravenous antibiotics within 14 days before the first dose of study drug.
7. Central nervous system involvement.
8. Diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
9. Evidence of current uncontrolled cardiovascular conditions within 6 months prior to randomization, including: Uncontrolled hypertension, cardiac arrhythmias, or congestive heart failure; Unstable angina, or Myocardial infarction.
10. 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.
11. Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
12. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (e.g., peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause).
13. Psychiatric illness/social situation that would limit compliance with study requirements.
14. Known allergy to any of the study medications.
15. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
16. Treatment with any investigational products within 60 days before randomization.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

705 participants in 2 patient groups, including a placebo group

Placebo + LenDex

Placebo Comparator group

Description:

Participants who were randomly assigned to receive placebo matching capsule single oral dose on Days 1, 8 and 15 along with standard regimen of LenDex (lenalidomide 25 mg capsules orally on Days 1-21 and dexamethasone 40 mg tablets orally on Days 1, 8, 15 and 22) for the first 18 cycles (each cycle was of 28 days). Following Cycle 18, participants received 3.0 mg ixazomib matching placebo capsule as single oral dose on Days 1, 8 and 15 along with lenalidomide 10 mg capsules orally on Days 1-21 in each 28-day cycle until progressive disease or unacceptable toxicity, whichever comes first up to end of study (up to approximately 109 months).

Treatment:

Drug: Lenalidomide

Drug: Dexamethasone

Drug: Placebo

Active Comparator: Ixazomib + LenDex

Active Comparator group

Description:

Participants who were randomly assigned to receive Ixazomib 4.0 mg capsule single oral dose on Days 1, 8 and 15 along with standard regimen of LenDex (lenalidomide 25 mg capsules orally on Days 1-21 and dexamethasone 40 mg tablets orally on Days 1, 8, 15 and 22) for the first 18 cycles (each cycle was of 28 days). Following Cycle 18, participants received 3.0 mg ixazomib capsule as single oral dose on Days 1, 8 and 15 along with lenalidomide 10 mg capsules orally on Days 1-21 in each 28-day cycle until progressive disease or unacceptable toxicity, whichever comes first up to end of study (up to approximately 109 months).

Treatment:

Drug: Ixazomib

Drug: Lenalidomide

Drug: Dexamethasone