A Phase 1 Study of Ruxolitinib, Steroids and Lenalidomide for Relapsed/Refractory Multiple Myeloma (RRMM) Patients

NCT03110822 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: I-RUX-15-04
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 13

Brief Summary

This is a phase 1, multicenter, open-label study evaluating the safety and efficacy of ruxolitinib, steroids and lenalidomide among MM patients who currently show progressive disease.

Conditions

Multiple Myeloma

Keywords

Ruxolitinib; Steroids; Lenalidomide; Relapsed/Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Determination of maximum tolerated dose (MTD) of ruxolitinib in combination with steroids and lenalidomide [Tolerability].

  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.

  30 months

• Incidence of Treatment-Emergent Adverse Events [Safety]

  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

  54 months

Secondary Outcomes (8)

• Overall response rate (ORR) as a measure of efficacy

  54 months

• Clinical benefit rate (CBR) as a measure of efficacy

  54 months

• Progression Free Survival (PFS)

  54 months

• Assessment of the time to response as a measure of efficacy (TTR)

  54 months

• Assessment of the duration of response as a measure of efficacy (DOR)

  54 months

Study Arms (4)

Rux Len and Steroid

EXPERIMENTAL

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)

Drug: Ruxolitinib Oral Tablet [Jakafi]; Drug: Lenalidomide; Drug: Methylprednisolone

Rux and Steroid until progression, then add Len

EXPERIMENTAL

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.

Drug: Ruxolitinib Oral Tablet [Jakafi]; Drug: Lenalidomide; Drug: Methylprednisolone

Expanded Eligibility Criteria

EXPERIMENTAL

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]; Drug: Lenalidomide; Drug: Methylprednisolone

High-dose Ruxolitinib

EXPERIMENTAL

Subject will receive Ruxolitinib Oral Tablet \[Jakafi\] at 20mg BID and Methylprednisolone at 40mg QOD until disease progression.

Drug: Ruxolitinib Oral Tablet [Jakafi]; Drug: Methylprednisolone

Interventions

Ruxolitinib Oral Tablet [Jakafi] DRUG

Ruxolitinib will be administered on days 1-28 of the treatment cycle.

Also known as: Ruxolitinib, Jakavi

Expanded Eligibility Criteria; High-dose Ruxolitinib; Rux Len and Steroid; Rux and Steroid until progression, then add Len

Lenalidomide DRUG

Lenalidomide will be administered on Days 1-21 of the treatment cycle.

Also known as: Revlimid

Expanded Eligibility Criteria; Rux Len and Steroid; Rux and Steroid until progression, then add Len

Methylprednisolone DRUG

Methyl-prednisolone will be administered on Days 1-28 of the treatment cycle.

Also known as: Depo-Medrol, Solu-Medrol, Methyl Prednisolonate

Expanded Eligibility Criteria; High-dose Ruxolitinib; Rux Len and Steroid; Rux and Steroid until progression, then add Len

Eligibility Criteria

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

You may qualify if:

• \. 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
• minor criteria 1, 2, and 3, or 1, 2, and 4

You may not qualify if:

• 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
• 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).

Sponsors & Collaborators

• Oncotherapeutics: lead
• Incyte Corporation: collaborator

Study Sites (13)

Global Oncology, Inc.

Alhambra, California, 91801, United States

RECRUITING

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309-0633, United States

ACTIVE NOT RECRUITING

California Cancer Associates for Research & Excellence (cCARE)

Encinitas, California, 92024, United States

RECRUITING

Compassionate Care Research Group, Inc.

Fountain Valley, California, 92708, United States

TERMINATED

Robert A. Moss, M.D., F.A.C.P., Inc.

Fountain Valley, California, 92708, United States

TERMINATED

Pacific Cancer Care

Monterey, California, 93940, United States

TERMINATED

Sansum Clinic- Ridley-Tree Cancer Center

Santa Barbara, California, 93105, United States

TERMINATED

Wellness Oncology and Hematology

West Hills, California, 91307, United States

RECRUITING

James R. Berenson M.D. Inc.

West Hollywood, California, 90069, United States

RECRUITING

Cancer Specialists, LLC

Jacksonville, Florida, 32256, United States

RECRUITING

Millennium Oncology Research Clinic

Pembroke Pines, Florida, 33024, United States

TERMINATED

Regional Cancer Care Associates (RCCA) MD, LLC

Bethesda, Maryland, 20817, United States

ACTIVE NOT RECRUITING

Northwest Medical Specialists, PPLC

Tacoma, Washington, 98405, United States

WITHDRAWN

Related Publications (4)

• Berenson JR, Limon A, Rice S, Safaie T, Boccia R, Yang H, Moezi M, Lim S, Schwartz G, Eshaghian S, Brobeck M, Swift R, Eades BM, Bujarski S, Sebhat Y, Ray R, Kim S, Del Dosso A, Vescio R. A Phase I Trial Evaluating the Addition of Lenalidomide to Patients with Relapsed/Refractory Multiple Myeloma Progressing on Ruxolitinib and Methylprednisolone. Target Oncol. 2024 May;19(3):343-357. doi: 10.1007/s11523-024-01049-w. Epub 2024 Apr 20.

  PMID: 38643346 DERIVED

• Berenson JR, Martinez D, Safaie T, Boccia R, Yang H, Moezi M, Lim S, Schwartz G, Eshaghian S, Swift R, Eades BM, Bujarski S, Regidor B, Kim C, Kim S, Vescio R. Ruxolitinib and methylprednisolone for treatment of patients with relapsed/refractory multiple myeloma. Br J Haematol. 2023 Mar;200(6):722-730. doi: 10.1111/bjh.18593. Epub 2022 Dec 9.

  PMID: 36482815 DERIVED

• Berenson JR, Kim C, Bujarski S, To J, Spektor TM, Martinez D, Turner C, Ghermezi M, Eades BM, Swift RA, Schwartz G, Eshaghian S, Moss RA, Lim S, Vescio R. A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory multiple myeloma patients. Hematol Oncol. 2022 Dec;40(5):906-913. doi: 10.1002/hon.3066. Epub 2022 Aug 14.

  PMID: 35946431 DERIVED

• Berenson JR, To J, Spektor TM, Martinez D, Turner C, Sanchez A, Ghermezi M, Eades BM, Swift RA, Schwartz G, Eshaghian S, Stampleman L, Moss RA, Lim S, Vescio R. A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed/Refractory Multiple Myeloma. Clin Cancer Res. 2020 May 15;26(10):2346-2353. doi: 10.1158/1078-0432.CCR-19-1899. Epub 2020 Jan 14.

  PMID: 31937615 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ruxolitinib; Lenalidomide; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; methyl prednisolonate

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; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• James R Berenson, MD

  Oncotherapeutics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James R Berenson, MD

CONTACT

(310)623-1223; jberenson@berensoncancercenter.com

Afra Yehwalashet

CONTACT

ayehu@oncotherapeutics.com

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: February 27, 2017
• First Posted: April 12, 2017
• Study Start: February 1, 2017
• Primary Completion: September 1, 2024
• Study Completion (Estimated): February 1, 2027
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)