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

NCT02943473 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: GCO 16-1867
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

High Risk Smoldering Multiple Myeloma

Keywords

Smoldering multiple myeloma; myeloma; smoldering; ibrutinib

Outcome Measures

Primary Outcomes (1)

• Number of Patients Without Symptomatic Myeloma

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

  up to 1 year

Secondary Outcomes (10)

• Overall Response Rate

  up to 1 year

• Bone Density Changes

  baseline and one year

• PET-MRI Changes

  baseline and one year

• Change in Serum Interleukin-6 (IL-6)

  baseline and up to one year

• Change in Serum Stromal Cell-derived Factor-1 (SDF-1)

  baseline and up to one year

Study Arms (1)

Ibrutinib

EXPERIMENTAL

Ibrutinib (trademark name is IMBRUVICA®). 560 mg dose administered on a continuous basis

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Ibrutinib is a type of drug called a "kinase inhibitor." Kinases are proteins inside cells that help cells live and grow. Ibrutinib blocks a specific kinase protein in our bodies. This protein is thought to be very important in helping blood cancer cells live and grow. By blocking this kinase protein, ibrutinib stops cancer cells from growing.

Also known as: IMBRUVICA

Ibrutinib

Eligibility Criteria

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

You may qualify if:

• High risk SMM, defined as follows by Mayo Clinic criteria:
• Bone marrow plasma cells between 10% and 60%
• Serum M-protein ≥ 3 g/dL \[except IgA ≥ 2 g/dL\] or urine M-protein \> 500 mg per 24 hours
• Serum free light chain ratio \< 0.126 or \> 8; an involved to uninvolved ratio of ≥ 100 is permitted
• Measurable disease, defined as: M-protein ≥ 1 g/dL OR Bence-Jones protein (BJP) \> 200 mg/24 hr OR involved free light chain \> 100 mg/dL
• Diagnosed with SMM within the last 4 years
• Laboratory
• Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening, with the exception of pegylated G-CSF (pegfilgrastim) and darbopoetin which require at least 14 days prior to screening defined as:
• Absolute neutrophil count \> 750 cells/mm3 (1.0 x 109/L).
• Platelet count \> 75,000 cells/mm3 (75 x 109/L).
• Adequate hepatic and renal function defined as:
• Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN).
• Estimated creatinine clearance ≥ 30 ml/min (Cockcroft-Gault)
• Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, in which case the total bilirubin should be \< 3 x ULN)
• PT/INR \< 1.5 x ULN and PTT (aPTT) \< 1.5 x ULN

You may not qualify if:

• No end organ damage attributable to a plasma cell disorder, defined as having ANY of the following:
• Hypercalcemia: Serum calcium \> 1 mg/dL above the upper limit of normal or \> 11 mg/dL
• Renal insufficiency: Serum creatinine \> 2 mg/dL or creatinine clearance \< 30 mL per min
• Anemia: Hemoglobin value \> 2 g/dL below the upper limit of normal or a hemoglobin value \< 10 g/dL
• Bone lesions: One or more lytic lesions on skeletal radiography, CT, MRI, PET-CT, or PET-MRI
• Bone marrow plasma cells \< 10% or \> 60%
• Has received prior anti-myeloma therapy of any type
• Has received prior bisphosphonate therapy
• Has received an investigational drug, investigational vaccine, or has used an investigational medical device within 4 weeks or 4 half-lives, whichever is longer, before Cycle 1, Day 1 of study therapy
• Osteoporosis, defined as having a T-score on DEXA of ≤ -2.5
• Concurrent Conditions
• History of other malignancies, except:
• Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Pharmacyclics LLC.: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Smoldering Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Histologic Type

Results Point of Contact

• Title: Dr. Ajai Chari
• Organization: Icahn School of Medicine at Mount Sinai

ajai.chari@mountsinai.org

(212) 241-7873

Study Officials

• Ajai Chari, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 21, 2016
• First Posted: October 24, 2016
• Study Start: May 18, 2017
• Primary Completion: September 10, 2019
• Study Completion: September 10, 2019
• Last Updated: December 16, 2020
• Results First Posted: December 16, 2020

Record last verified: 2020-11

Locations

US (1)