A Phase 1 Study of Ruxolitinib, Steroids and Lenalidomide for Relapsed/Refractory Multiple Myeloma (RRMM) Patients
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ClinicalTrials.gov Identifier: NCT03110822 |
Recruitment Status :
Recruiting
First Posted : April 12, 2017
Last Update Posted : April 20, 2022
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Condition or disease | Intervention/treatment | Phase |
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Multiple Myeloma | Drug: Ruxolitinib Oral Tablet [Jakafi] Drug: Lenalidomide Drug: Methylprednisolone | Phase 1 |

Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 134 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | There are 4 study parts: Dose escalation and expansion (Study Part 1), Ruxolitinib/Methylprednisolone Arm (Study Part 2), Expanded Eligibility Criteria (Study Part 3), and High Dose (Study Part 4). The first 49 subjects will be enrolled into the Ruxolitinib, Lenalidomide and Methylprednisolone treatment arm (Study Part 1). Subjects in Study Part 2 will receive Ruxolitinib and Methylprednisolone until confirmed disease progression. Lenalidomide will be added to the treatment once disease progression is confirmed. Subjects in Study Part 3 will receive Ruxolitinib, Lenalidomide and Methylprednisolone treatment. Subjects in Study Part 4 will receive high-dose Ruxolitinib and Methylprednisolone treatment. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1 Study of Ruxolitinib, Steroids and Lenalidomide for Relapsed/Refractory Multiple Myeloma (RRMM) Patients |
Actual Study Start Date : | February 1, 2017 |
Estimated Primary Completion Date : | September 2022 |
Estimated Study Completion Date : | February 2027 |

Arm | Intervention/treatment |
---|---|
Experimental: Rux Len and Steroid
Ruxolitinib Oral Tablet [Jakafi] at 5mg, 10mg or 15mg BID, Lenalidomide Oral at 5mg or 10mg QD and Methylprednisolone Oral at 40mg QOD. (Dose varies during dose escalation portion of the study)
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Drug: Ruxolitinib Oral Tablet [Jakafi]
Ruxolitinib will be administered on days 1-28 of the treatment cycle.
Other Name: Ruxolitinib, Jakavi Drug: Lenalidomide Lenalidomide will be administered on Days 1-21 of the treatment cycle.
Other Name: Revlimid Drug: Methylprednisolone Methyl-prednisolone will be administered on Days 1-28 of the treatment cycle.
Other Name: Depo-Medrol, Solu-Medrol, Methyl Prednisolonate |
Experimental: Rux and Steroid until progression, then add Len
Subject will receive Ruxolitinib Oral Tablet [Jakafi] at 15mg BID, and Methylprednisolone at 40mg QOD until disease progression. Lenalidomide at 10mg QD will be added to the treatment (Ruxolitinib, Methylprednisolone) once disease progression was confirmed.
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Drug: Ruxolitinib Oral Tablet [Jakafi]
Ruxolitinib will be administered on days 1-28 of the treatment cycle.
Other Name: Ruxolitinib, Jakavi Drug: Lenalidomide Lenalidomide will be administered on Days 1-21 of the treatment cycle.
Other Name: Revlimid Drug: Methylprednisolone Methyl-prednisolone will be administered on Days 1-28 of the treatment cycle.
Other Name: Depo-Medrol, Solu-Medrol, Methyl Prednisolonate |
Experimental: Expanded Eligibility Criteria
Subject will receive Ruxolitinib Oral Tablet [Jakafi] at 15mg BID, Lenalidomide at 10mg QD, and Methylprednisolone at 40mg QOD until disease progression.
|
Drug: Ruxolitinib Oral Tablet [Jakafi]
Ruxolitinib will be administered on days 1-28 of the treatment cycle.
Other Name: Ruxolitinib, Jakavi Drug: Lenalidomide Lenalidomide will be administered on Days 1-21 of the treatment cycle.
Other Name: Revlimid Drug: Methylprednisolone Methyl-prednisolone will be administered on Days 1-28 of the treatment cycle.
Other Name: Depo-Medrol, Solu-Medrol, Methyl Prednisolonate |
Experimental: High-dose Ruxolitinib
Subject will receive Ruxolitinib Oral Tablet [Jakafi] at 20mg BID and Methylprednisolone at 40mg QOD until disease progression.
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Drug: Ruxolitinib Oral Tablet [Jakafi]
Ruxolitinib will be administered on days 1-28 of the treatment cycle.
Other Name: Ruxolitinib, Jakavi Drug: Methylprednisolone Methyl-prednisolone will be administered on Days 1-28 of the treatment cycle.
Other Name: Depo-Medrol, Solu-Medrol, Methyl Prednisolonate |
- Determination of maximum tolerated dose (MTD) of ruxolitinib in combination with steroids and lenalidomide [Tolerability]. [ Time Frame: 30 months ]MTD will be determined by measuring incidence of the dose-limiting toxicities (DLTs) per dose level, of ruxolitinib in combination with steroids and lenalidomide for MM patients currently with progressive disease.
- Incidence of Treatment-Emergent Adverse Events [Safety] [ Time Frame: 54 months ]Safety will be measured by counting the occurrence of adverse events throughout the study, graded via Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria
- Overall response rate (ORR) as a measure of efficacy [ Time Frame: 54 months ]Overall response rate (ORR) is defined as CR + VGPR + PR
- Clinical benefit rate (CBR) as a measure of efficacy [ Time Frame: 54 months ]Clinical benefit rate is defined as ORR + MR
- Progression Free Survival (PFS) [ Time Frame: 54 months ]Progression-free survival will be measured in months as the time from initiation of therapy to progressive disease or death from any cause, whichever occurs first
- Assessment of the time to response as a measure of efficacy (TTR) [ Time Frame: 54 months ]Time to response, defined as the time from the initiation of therapy to the first evidence of confirmed clinical benefit defined as > minimal response (MR, including patients who achieved a complete response (CR), very good partial response (VGPR), partial response (PR), or MR
- Assessment of the duration of response as a measure of efficacy (DOR) [ Time Frame: 54 months ]Duration of response, defined as the time (in months) from the first response to progressive disease
- Assessment of the overall survival (OS) as a measure of efficacy [ Time Frame: 54 months ]Overall survival, defined as the time (in months) from initiation of therapy to death from any cause or last follow-up visit
- Assessment of the time to progression as a measure of efficacy (TTP) [ Time Frame: 54 months ]Time to progression, defined as the time (in months) from the initiation of therapy to progressive disease.
- Assessment of response in additional cohorts [ Time Frame: 54 months ]
Response to initial therapy (ruxolitinib and methylprednisolone alone) will be compared to the response to therapy with addition of lenalidomide (ruxolitinib, lenalidomide, methylprednisolone).
Response to higher dose of ruxolitinib (20 mg BID) with steroids, the response will be compared to the initial response to therapy of patients treated with ruxolitinib (15 mg BID) alone with steroids as well as to the therapy with addition of lenalidomide (ruxolitinib, lenalidomide, methylprednisolone).

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible to enroll in this study.
1. Has a diagnosis of MM based on standard criteria as follows:
Major criteria:
- Plasmacytomas on tissue biopsy.
- Bone marrow plasmacytosis (greater than 30% plasma cells).
- Monoclonal immunoglobulin spike on serum electrophoresis IgG greater than 3.5 g/dL or IgA greater than 2.0 g/dL or kappa or lambda light chain excretion greater than 1 g/day on 24 hour urine protein electrophoresis.
Minor criteria:
- bone marrow plasmacytosis (10% to 30% plasma cells)
- monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
- lytic bone lesions
- normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600 mg/dL
Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:
- any 2 of the major criteria
- major criterion 1 plus minor criterion 2, 3, or 4
- major criterion 3 plus minor criterion 1 or 3
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minor criteria 1, 2, and 3, or 1, 2, and 4
2. Currently has MM with measurable disease, defined as:
- a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL and/or
- urine monoclonal protein levels of at least 200mg/24 hours
- for patients without measurable serum and urine M-protein levels, an involved SFLC > 100 mg/L or abnormal SFLC ratio
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for patients with IgD MM, a monoclonal immunoglobulin IgD of at least 1500 mg/L or meet other measurable disease eligibility criteria
3. Currently has progressive MM
MM patients that are relapsed or have refractory disease from at least 2 regimens or lines of therapy including an IMID and a proteasome inhibitor, are eligible for enrollment provided they fulfill the other eligibility criteria:
- Patients are considered relapsed, when they progress greater than 8 weeks from their last dose of treatment.
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Patients are refractory when they progress while currently receiving the treatment or within 8 weeks of its last dose.
4. Previous exposure to lenalidomide independent of the response
5. The patient is not a candidate for a transplant
6. Understand and voluntarily sign an informed consent form before receiving any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn at any time without prejudice to their future medical care.
7. Able to adhere to the study visit schedule and other protocol requirements
8. ECOG performance status of ≤ 2 at study entry
9. Life-expectancy of greater than 3 months
10. Laboratory test results within these ranges at Screening and confirmed at enrollment prior to drug dosing on Cycle 1, Day 1:
- Absolute neutrophil count ≥ 1.5 x 10E9/L; if the bone marrow is extensively infiltrated ( ≥ 70% plasma cells) then ≥ 1.0 x 10E9/L
- Platelet count ≥ 75 x 10E9/L; if the bone marrow is extensively infiltrated ( ≥ 70% plasma cells) then ≥ 50 x 10E9/L patients must not have received platelet transfusion for at least 7 days prior to receiving screening platelet count. If patient have creatinine clearance of less than 60mL/min, patient's platelet count must be greater than 150 x 10E9/L.
- Hemoglobin ≥ 8.0 g/dL within 21 days prior to enrollment. 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.
- Calculated or measured creatinine clearance (CrCl) of > 60 mL/minute (Study Part 1,2,3(2), and 4) or 30 to ≤ 60 mL/minute (Part 3(1)) as calculated by Cockcroft-Gault method (Appendix 3).
- Total bilirubin levels ≤ 2.0 mg/dL (normal levels)
- AST (SGOT) and ALT (SGPT) ≤ 2 x ULN
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Serum potassium 3.0 - 5.5 mEq/L
11. Patients must be registered into the mandatory REVLIMID REMS™ program, and be willing and able to comply with the requirements of the REVLIMID REMS™ program
12. FCBP† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting ruxolitinib and must either commit to continued abstinence from heterosexual intercourse or use acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts taking ruxolitinib with or without lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
† A FCBP (female of childbearing potential) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
13. Able to take aspirin (acetylsalicylic acid, ASA) at 81 or 325 mg/daily as antiplatelet therapy if platelet count is above 30 x 10E9/L (subjects intolerant to ASA may use warfarin or low molecular weight heparin)
Exclusion Criteria:
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Subjects meeting any of the following exclusion criteria are not to be enrolled in the study:
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (> 2.0 × 10E9/L circulating plasma cells by standard differential)
- Primary amyloidosis
- Non-hematologic malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
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Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
- Myocardial infarction within 6 months prior to enrollment
- New York Heart Association (NYHA) Class II or greater heart failure or uncontrolled angina
- Clinically significant pericardial disease
- Severe uncontrolled ventricular arrhythmias
- Echocardiogram or MUGA evidence of LVEF below institutional normal within 28 days prior to enrollment
- Electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Severe hypercalcemia, i.e., serum calcium ≥ 12 mg/dL (3.0 mmol/L) corrected for albumin
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- Undergone major surgery within 28 days prior enrollment or has not recovered from side effects of such therapy (vertebroplasty or kyphoplasty is not considered to be a major surgery; however, the investigator is to discuss enrollment of a subject with a recent history of kyphoplasty with the medical monitor).
- Pregnant or breast feeding females (lactating females must agree not to breast feed while taking lenalidomide)
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Received the following prior therapy:
- Chemotherapy within 3 weeks of study drugs
- Corticosteroids (>20 mg/daily prednisone or equivalent) within 3 weeks of study drugs to ensure that steroid dose intensity at the beginning of the treatment is not altered by administration of steroids prior to the study. Consumption of steroids within 3 weeks of the treatment may interfere with efficacy and side effects due to differences of steroid intensity.
- Immunotherapy or antibody therapy as well as thalidomide, arsenic trioxide, or bortezomib within 21 days before study drugs
- Lenalidomide within 7 days before study drugs
- Lenalidomide within 21 days before study drugs (Part 4 only)
- Extensive radiation therapy within 28 days before study drugs. Receipt of localized radiation therapy does not preclude enrollment.
- Use of any other experimental drug or therapy within 28 days of study drugs
- Strong CYP3A4 inhibitors, strong CYP3A4 inducers and fluconazole doses >200 mg daily within 5 half-lives before study drugs. (For example, clarithromycin has half-life of 4 hours so washout period for clarithromycin is 20 hours.)
- Known hypersensitivity to compounds of similar chemical or biological composition to thalidomide and lenalidomide or steroids.
- Concurrent use of other anti-cancer agents or treatments
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
- Known positivity for human immunodeficiency virus (HIV), hepatitis B or C, and /or active tuberculosis (TB) including subjects with latent TB or with the risk factor for activation of latent TB.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03110822
Contact: James R Berenson, MD | (310)623-1223 | jberenson@berensoncancercenter.com | |
Contact: Afra Yehwalashet | ayehu@oncotherapeutics.com |
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United States, Florida | |
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Contact: Mary A Anderson MaryAlice.Anderson@CSNF.US | |
Contact: Amanda Fallon Amanda.Fallon@CSNF.us | |
Principal Investigator: Mehdi M Moezi, MD | |
Millennium Oncology Research Clinic | Terminated |
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Contact: Natalie Bongiorno, RN 301-571-2016 nbongiorno@regionalcancercare.org | |
Principal Investigator: Ralph Boccia, MD | |
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Northwest Medical Specialists, PPLC | Recruiting |
Tacoma, Washington, United States, 98405 | |
Contact: Sue Quinsey squinsey@nwmsonline.com | |
Principal Investigator: Jorge M Chaves, MD |
Principal Investigator: | James R Berenson, MD | Oncotherapeutics |
Responsible Party: | Oncotherapeutics |
ClinicalTrials.gov Identifier: | NCT03110822 |
Other Study ID Numbers: |
I-RUX-15-04 |
First Posted: | April 12, 2017 Key Record Dates |
Last Update Posted: | April 20, 2022 |
Last Verified: | April 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Ruxolitinib Steroids Lenalidomide Relapsed/Refractory Multiple Myeloma |
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Methylprednisolone |
Methylprednisolone Acetate Methylprednisolone Hemisuccinate Prednisolone Prednisolone acetate Lenalidomide Prednisolone hemisuccinate Prednisolone phosphate Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents Anti-Inflammatory Agents |