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

Completed · Phase 1

Conditions studied: Refractory Multiple Myeloma, Multiple Myeloma in Relapse, Multiple Myeloma

In brief

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.

Key facts

Study ID

NCT03702725

Run by

Alliance Foundation Trials, LLC.

People needed

14

Starts

2019-08-29

Expected to finish

2024-10-04

Last updated by the study team

2026-01-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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%).
• Hemoglobin level ≥ 8 g/dL, independent of transfusion support.
• Biochemical values must be within the following limits within 7 days prior to registration
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin).
• Serum creatinine ≤ 2 x ULN or GFR > 30 ml/min based on either the estimated Glomerular Filtration Rate (Crockcoft Gault) or measured GFR from 24-hour urine sample. Study participants with GFR 30-50 ml/min will be treated according to manufacturer's instruction with lenalidomide 10mg rather than 25 mg.
• Ability to understand and willingness to sign a written informed consent form (ICF).
• Ability to adhere with the study visit schedule and other protocol procedures.
• A negative pregnancy test will be required for all women of child bearing potential within 7 days prior to registration. Breast feeding is not permitted.
• Fertility requirements
• Female patients with child bearing potential must have a negative pregnancy test at least 7 days before starting treatment drugs.

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.
• Currently active systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Use of antibiotics for treatment of infection within 14 days prior to registration
• Recent infection requiring systemic treatment that was completed within 14 days of registration.
• Known infection with human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or any uncontrolled active systemic infection.
• Note: Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result within 14 days prior to registration.
• History of stroke or intracranial hemorrhage within 6 months prior to registration.
• Patients who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or patient who requires continuous treatment with a strong CYP3A inhibitor (Appendix II).
• Currently active, clinically significant hepatic impairment (Child-Pugh class B or C) according to the Child Pugh classification (Appendix III).
• Lactating or pregnant
• Major surgery within 4 weeks prior to registration

Where it is running

• Loyola University Medical Center — Maywood, Illinois, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Wake Forest Baptist Comprehensive Cancer Center — Winston-Salem, North Carolina, United States
• The Ohio State University Wexner Medical Center/James Cancer Hospital — Columbus, Ohio, United States
• Rhode Island Hospital — Providence, Rhode Island, United States

Full record on ClinicalTrials.gov

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