Study of Ibrutinib in Combination With Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma

NCT03702725 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: AFT-15
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 5

Brief Summary

This is a registration, open-label phase 1 study of the combination of ibrutinib/lenalidomide:/dexamethasone in women and men with relapsed/refractory multiple myeloma.

Conditions

Refractory Multiple Myeloma; Multiple Myeloma in Relapse; Multiple Myeloma

Keywords

Myeloma; Multiple Myeloma; Refractory Multiple Myeloma; Ibrutinib

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities

  DLTs were grade 4 thrombocytopenia; grade 4 neutropenia lasting \> 5 days or febrile neutropenia; grade 3 thrombocytopenia with bleeding or platelet transfusion; grade 3-4 hyperglycemia or a thrombotic/embolic event; or grade 3-4 non-hematologic toxicity (except grade 3 nausea, diarrhea, and vomiting), that were at least probably related to treatment, treatment delays ≥ 21 days for toxicity, and treatment-related death.

  During cycle 1 (28-day cycle)

• Maximum Toxicity Grade

  The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (Grade 3 or higher) will be determined. Adverse Events were graded using CTCAE v4.0.

  Up to 34 month

Secondary Outcomes (4)

• Progression Free Survival

  34 Months

• Overall Survival

  34 Months

• Duration of Response

  34 Months

• Objective Response Rate

  Up to 34 months

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Dose escalation will consist of three different drug levels of Ibrutinib, Lenalidomide, and Dexamethasone. Dose Escalation (Ibrutinib, Lenalidomide, Dexamethasone Combination)

Drug: Ibrutinib; Drug: Lenalidomide; Drug: Dexamethasone

Dose Expansion

EXPERIMENTAL

Dosage of the combination will depend on the determine of maximum tolerated dose learned from the Dose Escalation phase. Dose Expansion (Ibrutinib, Lenalidomide, Dexamethasone Combination)

Drug: Ibrutinib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Ibrutinib DRUG

Ibrutinib administered on every day of each 28 day cycle. Dosage depends on timing of patient enrollment and dosage tolerance by patients already enrolled.

Also known as: Imbruvica

Dose Escalation; Dose Expansion

Lenalidomide DRUG

Lenalidomide administered on days 1-21 of each 28 day cycle. Dosage depends on findings from Dose Escalation phase.

Also known as: Revlimid

Dose Escalation; Dose Expansion

Dexamethasone DRUG

Dexamethasone administered on days 1, 8, 15, and 22 of every 28 day cycle. Dosage depends on findings from Dose Escalation phase.

Also known as: Decadron

Dose Escalation; Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Men and women ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Appendix I).
• Symptomatic multiple myeloma (MM) (as defined by revised IMWG criteria) with measurable disease, defined here as having at least one of the following:
• Serum monoclonal protein ≥ 0.5 g/dL
• ≥200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum immunoglobulin free light chain (FLC): involved FLC ≥ 10 mg/dL (≥ 100 mg/L) AND abnormal serum immunoglobulin kappa to lambda free light chain ratio.
• At least 1 prior therapy with demonstrated disease progression following the most recent line of treatment.
• Progression of disease within 60 days of completion of last therapeutic regimen or the failure to achieve minimal response while on last treatment (according to IMWG).
• Patients should not have progressed on lenalidomide at a dose of more than 10mg
• No prior treatment with ibrutinib or any other protein kinase inhibitory drug or drug targeting the b-cell receptor (BCR) signal transduction pathway.
• Patients with prior daratumumab and allogeneic stem cell transplant are included.
• PT/INR \<1.5 x ULN and PTT (aPTT) \<1.5 x ULN, except if on anticoagulation for medical reasons in which case INR should be ≤ 3
• Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to registration, with the exception of pegylated G-CSF (pegfilgrastim) and darbopoeitin which require at least 14 days prior to screen and enrollment defined as:
• Absolute neutrophil count (ANC) ≥1000/mm3 independent of growth factor support.
• Transfusion independent platelet counts ≥75,000/mm3 (or ≥50,000/mm3 if bone marrow involvement is ≥50%).

You may not qualify if:

• Prior history of: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, osteosclerotic myeloma, Crow-Fukase syndrome, primary amyloidosis or plasma cell leukemia.
• Radiotherapy within 21 days of registration. However, if the radiation portal was localized to single lesion or fracture site and covered by ≤ 5% of the bone marrow reserve (by investigator estimate), the subject may be enrolled irrespective of the end date of radiotherapy.
• Prior chemotherapy:
• Alkylators (e.g. melphalan, cyclophosphamide) ≤ 21 days prior to registration and/or monoclonal antibody ≤ 6 weeks prior to first administration of study treatment.
• Anthracyclines ≤ 21 days prior to registration.
• High dose corticosteroids, immune modulatory drugs (thalidomide or lenalidomide), or proteasome inhibitors (bortezomib or carfilzomib) ≤ 14 days prior to registration.
• No concomitant high dose corticosteroids (concurrent use of corticosteroids). EXCEPTION: Patients may be on chronic steroids (maximum dose 10 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc.
• Currently active, clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration or baseline QTcF of \> 470.
• Unable to swallow capsules or disease significantly affecting gastrointestinal function, such as malabsorption syndrome, resection of the stomach or small bowel, or complete bowel obstruction.
• History of prior malignancy, with the exception of the following:
• Malignancy treated with curative intent and with no known active disease present for more than 3 years prior to registration and felt to be at low risk for recurrence by treating physician;
• Adequately treated non melanoma skin cancer or lentigo maligna without current evidence of disease; or
• Adequately treated breast or cervical carcinoma in situ without current evidence of disease.
• Peripheral neuropathy Grade \> 2 on clinical examination within 14 days prior to registration.
• Uncontrolled diabetes mellitus.

Sponsors & Collaborators

• Alliance Foundation Trials, LLC.: lead
• Pharmacyclics LLC.: collaborator

Study Sites (5)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State University Wexner Medical Center/James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

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MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

ibrutinib; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Jacob P. Laubach
• Organization: Dana Farber Cancer Institute

jacobp_laubach@dfci.harvard.edu

617-632-4218

Study Officials

• Evanthia Galanis, MD

  Alliance Foundation Trials, LLC.

  PRINCIPAL INVESTIGATOR

• Yvonne A. Efebera, MD

  Ohio State University Comprehensive Cancer Center

  STUDY CHAIR

• Jacob P. Laubach, MD

  Dana-Farber Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2018
• First Posted: October 11, 2018
• Study Start: August 29, 2019
• Primary Completion: September 27, 2024
• Study Completion: October 4, 2024
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)