Study of Lenalidomide/Ixazomib/Dexamethasone/Daratumumab in Transplant-Ineligible Patients With Newly Diagnosed MM

NCT04009109 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AFT-41
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 7

Brief Summary

A randomized Phase II clinical trial will be conducted to assess the impact on progression free survival (PFS) with the addition of ixazomib and daratumumab to lenalidomide as a maintenance treatment following induction with lenalidomide, ixazomib, dexamethasone, and daratumumab. Patients will be randomized to either: Arm A: 12 cycles of lenalidomide, ixazomib, daratumumab, and dexamethasone followed by lenalidomide until disease progression or unacceptable toxicity or a maximum of 2 years of maintenance therapy. Arm B: 12 cycles of lenalidomide, ixazomib, daratumumab and dexamethasone, followed by lenalidomide, ixazomib, and daratumumab until disease progression or unacceptable toxicity or a maximum of 2 years maintenance therapy.

Conditions

Myeloma, Multiple

Outcome Measures

Primary Outcomes (1)

• Impact of Study Treatment on Progression Free Survival (PFS)

  Time interval between registration and progression or death.

  5 Years

Secondary Outcomes (9)

• Minimal Residual Disease (MRD)

  5 Years

• Toxicity Profile of Treatment Arm Based on Patient Response

  5 Years

• Overall Response Rate (ORR)

  5 Years

• Overall Survival (OS)

  5 Years

• Quality of Life with the EQ 5D 5L Questionnaire

  5 Years

Other Outcomes (2)

• Changes in Body Composition After Induction Therapy

  5 Years

• Circulating MM cells and circulating DNA through DNA sequencing

  5 Years

Study Arms (2)

Lenalidomide

EXPERIMENTAL

12 cycles of lenalidomide, ixazomib, daratumumab, and dexamethasone followed by lenalidomide until disease progression or unacceptable toxicity or a maximum of 2 years of maintenance therapy.

Drug: Lenalidomide; Drug: Ixazomib; Drug: Daratumumab Injection; Drug: Dexamethasone

Lenalidomide, Ixazomib, Daratumumab, and Dexamethasone

EXPERIMENTAL

12 cycles of lenalidomide, ixazomib, dexamethasone, and daratumumab followed by lenalidomide, ixazomib, and daratumumab until disease progression or unacceptable toxicity or a maximum of 2 year maintenance therapy.

Drug: Lenalidomide; Drug: Ixazomib; Drug: Daratumumab Injection; Drug: Dexamethasone

Interventions

Lenalidomide DRUG

Induction and Maintenance

Also known as: Revlimid

Lenalidomide; Lenalidomide, Ixazomib, Daratumumab, and Dexamethasone

Ixazomib DRUG

Induction and Only Maintenance Arm B

Also known as: Ninlaro

Lenalidomide; Lenalidomide, Ixazomib, Daratumumab, and Dexamethasone

Daratumumab Injection DRUG

Induction and Only Maintenance Arm B

Also known as: Darzalex

Lenalidomide; Lenalidomide, Ixazomib, Daratumumab, and Dexamethasone

Dexamethasone DRUG

Induction and Only Maintenance Arm B

Also known as: Ozurdex

Lenalidomide; Lenalidomide, Ixazomib, Daratumumab, and Dexamethasone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be at least 18 years of age.
• Subject must have documented multiple myeloma:
• Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma
• Following CRAB features and/or myeloma-defining events (MDEs):
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
• Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL) OR
• Renal insufficiency: creatinine clearance \<40 mL per minute or serum creatinine \>177 mol/L (\>2 mg/dL) OR
• Anemia: hemoglobin value of \>2 g/dL below the lowest limit of normal, or a hemoglobin value \<100 g/L OR
• Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT. If bone marrow has \<10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement OR
• OR any one or more of the following biomarkers of malignancy (MDEs):
• Sixty percent (60%) or greater clonal plasma cells on bone marrow examination.
• Serum involved/uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100 mg/L (A patient's involved free light chain, either kappa or lambda, is the one that is above the normal reference range; the uninvolved free light chain is the one that is typically in, or below, the normal range).
• More than one focal lesion on MRI that is at least 5 mm or greater in size.
• Measurable disease as defined by any of the following:
• IgG myeloma: serum monoclonal paraprotein (M-protein) level ≥0.5 g/dL; or

You may not qualify if:

• Patient has primary AL amyloidosis.
• Prior history of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
• Prior or current systemic therapy or stem cell transplantation (SCT) for MM, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before initial dosing. 1 cycle or less of urgent systemic treatment may be allowed after discussion with the Study Chair.
• Patients undergoing treatment for a malignancy within 5 years prior to study enrollment with the exception of non-invasive malignancies that in the opinion of the site investigator are considered cured or have minimal risk of recurrence within 5 years. Patient must not have active concomitant, invasive malignancy. Note: patients on chronic hormonal therapy for localized breast or prostate cancer with no evidence for the primary malignancies or prostate cancer undergoing active surveillance can be included.
• Radiation therapy ≤14 days prior to C1D1.
• Plasmapheresis ≤28 days prior to C1D1.
• Exhibiting clinical signs of meningeal involvement of MM ≤28 days prior to screening.
• Known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume \[FEV\] in 1 second \<60% of predicted normal), persistent asthma, or a history of asthma ≤ 2 years prior to screening (intermittent asthma is allowed).
• Note: Patients with known or suspected COPD or asthma must have a FEV1 test within 28 days prior to screening.
• Patient has history or evidence of unstable/uncontrolled medical or psychiatric disorder, condition or disease (e.g., active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion.
• Clinically significant cardiac disease, including:
• myocardial infarction ≤1 year prior to screening, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV).
• uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 5.0 Grade ≥2) or clinically significant ECG abnormalities;
• lead ECG performed ≤28 days prior to screening showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \>470 msec.
• Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies, or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure) or known sensitivity to mammalian-derived products.

Sponsors & Collaborators

• Alliance Foundation Trials, LLC.: lead
• Janssen Scientific Affairs, LLC: collaborator
• Celgene Corporation: collaborator
• Takeda: collaborator

Study Sites (7)

Northern Light Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68152, United States

Location

SUNY Upstate Medical Center

Syracuse, New York, 13210, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Gibbs Cancer Center & Research Institute/Spartanburg Regional Healthcare

Spartanburg, South Carolina, 29303, United States

Location

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MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; ixazomib; daratumumab; Dexamethasone; Calcium Dobesilate

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Evanthia Galanis, MD

  Alliance Foundation Trials, LLC.

  PRINCIPAL INVESTIGATOR

• Andrew Yee, MD

  Massachusetts General Hospital

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: June 20, 2019
• First Posted: July 5, 2019
• Study Start: October 21, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)