Ph 2 Maintenance Trial: Ixazomib vs Ixazomib-Lenalidomide for MM Patients

NCT03733691 | Terminated Phase 2 FDA Drug

• 1 other identifier: X16108
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, Phase 2 study involving two arms evaluating the efficacy and safety of ixazomib alone and the combination of both ixazomib and lenalidomide as maintenance therapy for patients with multiple myeloma who have achieved at least partial response (PR) or better after receiving a bortezomib- and lenalidomide-containing combination front-line therapy.

Conditions

Newly Diagnosed Multiple Myeloma

Keywords

Multiple Myeloma; Front-line; Maintenance therapy

Outcome Measures

Primary Outcomes (2)

• PFS

  Progression Free Survival

  Through study completion, approximately 5 years

• Adverse events (AEs)

  Monitoring safety and tolerability via monitoring adverse events graded by CTCAE v5

  throughout the study completion, approximately 5 years

Secondary Outcomes (2)

• OS

  from time of initiation of maintenance therapy to death from any cause or last follow-up visit, up to 60 months

• Deepening of the response

  throughout the study, up to 60 months

Study Arms (2)

Ixazomib Only

EXPERIMENTAL

The prescribed dose administration of ixazomib in this study is 3mg orally on Days 1, 8, and 15 of a 28-day cycle.

Drug: Ixazomib

Ixazomib + Lenalidomide

EXPERIMENTAL

The prescribed dose administration of ixazomib in this study is 3mg orally on Days 1, 8, and 15 of a 28-day cycle. The prescribed dose administration of lenalidomide in this study is the same as the dose of the patient's front-line treatment taken in the last treatment cycle unless otherwise clinically indicated per investigator's discretion, taken orally on days 1-28 of a 28-day cycle. If patient was receiving lenalidomide at a higher dose than 10 mg, then the dose of lenalidomide on this study will be adjusted to 10 mg daily on days 1-28 of a 28-day cycle

Drug: Ixazomib; Drug: Lenalidomide

Interventions

Ixazomib DRUG

3 mg oral capsule, Days 1, 8 and 15 of 28-day cycles

Also known as: Ninlaro

Ixazomib + Lenalidomide; Ixazomib Only

Lenalidomide DRUG

Same dose as in the front-line treatment in the last treatment cycle, taken orally, on days 1-28 of a 28-day cycle.

Also known as: Revlimid

Ixazomib + Lenalidomide

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18 years or older.
• Patients must be receiving a frontline bortezomib- and lenalidomide-containing regimen for treatment of disease
• Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) grater or equal 1,000/mm3 and platelet count greater or equal 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 7 days prior to screening platelets or at investigator's discretion.
• Hemoglobin ≥ 8.0 g/dL. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion must have been at least 7 days prior to obtaining screening hemoglobin or at investigator's discretion.
• Total bilirubin less or equal 1.5 times the upper limit of the normal range (ULN).
• Calculated or measured creatinine clearance greater or equal 30 mL/min. Calculation is based on a standard Cockcroft and Gault formula (Section 14.2).
• AST (SGOT) and ALT (SGPT) less or equal 3 x ULN or less or equal 5 x ULN if hepatic metastases are present.
• LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Mitigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
• Patients must be transplant ineligible as determined by the treating physician.
• Patients must have a life-expectancy of more than 6 months.
• Patients must have a confirmed diagnosis of MM.
• Patients receiving front-line therapy must have achieved at least PR and have completed at least 6 cycles of treatment.
• The disease must have reached a plateau phase at the end of front-line treatment as demonstrated bythe same response (using IMWG criteria) in three consecutive tests with at least three weeks between each test.
• Patients must have received frontline treatment within 8 weeks of enrollment.

You may not qualify if:

• Patient is currently progressing on a bortezomib- and lenalidomide-containing regimen.
• Patients who have received more than 1 line of therapy (thus non-frontline treated patients).
• Patients who were exposed to ixazomib during frontline therapy.
• Patient has ¬\> Grade 3 peripheral neuropathy or Grade 2 with pain during the screening period.
• Patient has known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery within 14 days before enrollment or at investigator's discretion.
• Patients undergoing stem cell therapy (SCT) or those who are planned for SCT.
• Radiotherapy within 14 days before enrollment or investigator's discretion. If the involved field is small, 7 days or investigator's discretion will be considered a sufficient interval between treatment and administration of the study drugs. Receipt of localized radiation therapy does not preclude enrollment.
• Infection requiring systemic antibiotic therapy or other serious infection such as known active hepatitis B or C virus infection, known human immunodeficiency virus (HIV) positive within 14 days before of study enrollment or at investigator's discretion.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, NYHA Class III or IV heart failure, unstable angina, clinically significant pericardial disease or myocardial infarction within the past 6 months, unless subject has a pacemaker. Prior to study entry, any ECG abnormality at Screening must be documented by the investigator as not medically relevant.
• Frontline therapy within 14 days or at investigator's discretion of the first dose of study drugs.
• Systemic treatment, within 14 days before or at investigator's discretion of the first dose of study drugs, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort or Ginkgo biloba.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

Sponsors & Collaborators

• Oncotherapeutics: lead
• Takeda: collaborator

Study Sites (1)

James R Berenson, MD, Inc.

West Hollywood, California, 90069, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• James R. Berenson M Inc., MD

  Oncotherapeutics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A randomized, open label, Phase 2 study involving two arms evaluating the efficacy and safety of ixazomib monotherapy (with steroids if applicable) and the combination of ixazomib and lenalidomide (with steroids if applicable) as maintenance therapy for patients with MM who have achieved at least PR after receiving a bortezomib and lenalidomide (with steroids if applicable)-containing combination frontline therapy.

Study Record Dates

• First Submitted: November 2, 2018
• First Posted: November 7, 2018
• Study Start: March 1, 2019
• Primary Completion: October 19, 2023
• Study Completion: October 19, 2023
• Last Updated: October 25, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)