Pilot Study Using Changes in Serum BCMA to Determine Disease Progression in Multiple Myeloma

NCT06209606 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: I-RUX-20-52
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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 using BCMA to test progression.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Time to Disease Progression (TTP)

  * To establish the utility of using an increase in sBCMA levels \> 25% or IMWG criteria for disease progression to direct this therapeutic approach, TTP will be measured, where TTP is defined as a number of days between the start of treatment (cycle 1 day 1) and PD. PD is defined by either change in sBCMA (≥25% increase from its nadir levels) or by standard IMWG criteria (using sM-protein and SFLC assessments), whichever occurs first. PD will be confirmed by two consecutive tests. * Duration of response 1 (DOR1), defined as the time from the first response to progressive disease as determined by either changes in sBCMA or IMWG criteria (whichever occurs first) while patients are on ruxolitinib and methylprednisolone treatment * Duration of response 2 (DOR2), defined as the time from the first response to progressive disease as determined by standard IMWG criteria while patients on ruxolitinib, lenalidomide and methylprednisolone treatment

  54 months

Secondary Outcomes (2)

• Safety and Tolerability

  54 months

• Efficacy and Overall Response

  54 months

Study Arms (2)

Rux + Steroid

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: Methylprednisolone

Rux + Steroid + Len

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

Interventions

Ruxolitinib Oral Tablet [Jakafi] DRUG

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

Also known as: Ruxolitinib, Jakafi

Rux + Steroid; Rux + Steroid + Len

Lenalidomide DRUG

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

Also known as: Revlimid

Rux + Steroid + 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

Rux + Steroid; Rux + Steroid + 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:
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• Plasmacytomas on tissue biopsy
• BM 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:
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• BM 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

You may not qualify if:

• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia (\> 2.0 × 109/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
• Patients with uncontrolled infections
• 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 must 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

Sponsors & Collaborators

• Oncotherapeutics: lead
• Incyte Corporation: collaborator

Study Sites (1)

Berenson Cancer Center

West Hollywood, California, 90069, United States

RECRUITING

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 Berenson, MD

  Oncotherapeutics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard Bailey

CONTACT

310-464-2190; rbailey@oncotherapeutics.com

Yohana Sebhat, MPH

CONTACT

310-623-1222; ysebhat@oncotherapeutics.com

Study Design

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

Model Details: This is a pilot, multicenter, open-label study evaluating the utility of using increases in serum BCMA \> 25% versus IMWG criteria to determine disease progression among patients with RRMM treated with ruxolitinib and methylprednisolone to determine when to add lenalidomide to the regimen. Subjects that were treated with ruxolitinib with methylprednisolone and showed disease progression will have lenalidomide added to their regimen. PD is defined by either change in sBCMA (≥ 25% increase from nadir) or by standard IMWG criteria, whichever occurs first. PD will be confirmed by two consecutive tests.

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: January 17, 2024
• Study Start: December 8, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): February 1, 2029
• Last Updated: December 17, 2024

Record last verified: 2024-12

Locations

US (1)