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Study on the Effect of Ibrutinib on High Risk Smoldering Multiple Myeloma Patients

Phase 2
Terminated
Conditions
High Risk Smoldering Multiple Myeloma
Interventions
Registration Number
NCT02943473
Lead Sponsor
Icahn School of Medicine at Mount Sinai
Brief Summary

The purpose of this research study is to test whether the drug ibrutinib (trademark name: IMBRUVICA®) is effective at preventing the development of multiple myeloma in people who currently have smoldering myeloma. The researchers conducting this trial) have reason to believe that ibrutinib can delay the development of multiple myeloma, thus giving people who currently have smoldering myeloma a longer period of time when they feel healthy and well.

Smoldering myeloma is an abnormal condition that is considered to be an early phase of the disease multiple myeloma. In this disorder, there is an abnormal growth of plasma cells, which is a type of blood cell found in the bone marrow. This growth is not as severe in people with smoldering myeloma as it is in multiple myeloma, so people with smoldering myeloma do not have any symptoms and tend to feel well. However, they have a higher risk of developing multiple myeloma than people in the general population.

Some people with smoldering myeloma are at an especially high risk of developing myeloma - 50% of these people will develop multiple myeloma 2 years after they are diagnosed with smoldering myeloma. The investigators identify these people by looking at the amount of myeloma in the bone marrow (called "bone marrow plasma cell percentage") and the amount of myeloma protein (called "serum protein electrophoresis" and "serum free light chain assay") in the blood. To be considered high risk, individuals must have highly abnormal levels for these tests.

Based upon current guidelines, people with smoldering myeloma do not require any treatment. However, known is that many of these people will develop multiple myeloma in the near future. Currently there have been no proven and effective way of preventing these people from developing multiple myeloma, which remains an incurable disease.

Detailed Description

This is a phase 2, open-label, single center, prospective pilot study designed to assess the efficacy of ibrutinib in subjects with high risk smoldering multiple myeloma.

All enrolled subjects will be treated with ibrutinib 560 mg (4 capsules, each containing 140 mg) taken PO daily for 12 cycles (28 days each). If a subject demonstrates benefit from ibrutinib, therapy may be extended beyond 12 cycles to a maximum of 2 years. Subjects who progress and meet criteria for symptomatic multiple myeloma will be withdrawn from study.

An initial cohort of 15 subjects will be accrued. If 4 or more patients progress to symptomatic myeloma in one year, then the study will be reviewed with the FDA to determine whether to employ a higher dose of ibrutinib, or to stop for futility. Otherwise, 21 additional patients will be accrued for a total sample size of 36.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
9
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
IbrutinibIbrutinibIbrutinib (trademark name is IMBRUVICA®). 560 mg dose administered on a continuous basis
Primary Outcome Measures
NameTimeMethod
Number of Patients Without Symptomatic Myelomaup to 1 year

Disease response - the proportion of patients with high risk smoldering multiple myeloma who do not progress to symptomatic myeloma as defined by the IMWG.

Secondary Outcome Measures
NameTimeMethod
Change in Serum Interleukin-6 (IL-6)baseline and up to one year

Bone Related Biomarker Changes

Change in Serum Macrophage Inflammatory Protein-1α (MIP-1α)baseline and up to one year

Bone Related Biomarker Changes

Change in Serum C-terminal Telopeptide (CTX)baseline and up to one year

Bone Related Biomarker Changes

Bone Density Changesbaseline and one year

Changes in bone density, particularly in patients with osteopenia (defined as T-score on bone densitometry testing (DEXA) of -1 to -2.5).

PET-MRI Changesbaseline and one year

Changes in PET-MRI, particularly in patients with osteopenia

Change in Serum Stromal Cell-derived Factor-1 (SDF-1)baseline and up to one year

Bone Related Biomarker Changes

Change in Serum Dickkopf-1 (DKK-1)baseline and up to one year

Bone Related Biomarker Changes

Overall Response Rateup to 1 year

Overall response rate, defined as partial response or better per IMWG criteria. (IMWG response criteria are - Complete Response, Very good partial response, partial response, Minimal response, stable disease, and progressive disease)

Change in Serum Receptor Activator of Nuclear-factor Kappa B Ligand (RANKL)baseline and up to one year

Bone Related Biomarker Changes

Change in Urine N-terminal Telopeptide (NTx)baseline and up to one year

Bone Related Biomarker Changes

Trial Locations

Locations (1)

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

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