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Trial record 17 of 312 for:    IBRUTINIB

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

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ClinicalTrials.gov Identifier: NCT02943473
Recruitment Status : Recruiting
First Posted : October 24, 2016
Last Update Posted : March 22, 2019
Sponsor:
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Ajai Chari, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE October 21, 2016
First Posted Date  ICMJE October 24, 2016
Last Update Posted Date March 22, 2019
Study Start Date  ICMJE November 2016
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2016)
Number of patients without symptomatic myeloma [ Time Frame: up 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02943473 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2016)
  • Overall Response Rate [ Time Frame: up 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)
  • Bone Density Changes [ Time Frame: baseline 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 Changes [ Time Frame: baseline and one year ]
    Changes in PET-MRI, particularly in patients with osteopenia
  • Change in Serum interleukin-6 (IL-6) [ Time Frame: baseline and up to one year ]
    Bone Related Biomarker Changes
  • Change in Serum stromal cell-derived factor-1 (SDF-1) [ Time Frame: baseline and up to one year ]
    Bone Related Biomarker Changes
  • Change in Serum receptor activator of nuclear-factor kappa B ligand (RANKL) [ Time Frame: baseline and up to one year ]
    Bone Related Biomarker Changes
  • Change in Serum macrophage inflammatory protein-1α (MIP-1α) [ Time Frame: baseline and up to one year ]
    Bone Related Biomarker Changes
  • Change in Serum Dickkopf-1 (DKK-1) [ Time Frame: baseline and up to one year ]
    Bone Related Biomarker Changes
  • Change in Serum C-terminal telopeptide (CTX) [ Time Frame: baseline and up to one year ]
    Bone Related Biomarker Changes
  • Change in Urine N-terminal telopeptide (NTx) [ Time Frame: baseline and up to one year ]
    Bone Related Biomarker Changes
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study on the Effect of Ibrutinib on High Risk Smoldering Multiple Myeloma Patients
Official Title  ICMJE A Phase 2 Study of the Effect of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib on Disease Response in Patients With High Risk Smoldering Multiple Myeloma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE High Risk Smoldering Multiple Myeloma
Intervention  ICMJE Drug: Ibrutinib
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.
Other Name: IMBRUVICA
Study Arms  ICMJE Experimental: Ibrutinib
Ibrutinib (trademark name is IMBRUVICA®). 560 mg dose administered on a continuous basis
Intervention: Drug: Ibrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 21, 2016)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria Disease Related

  1. High risk SMM, defined as follows by Mayo Clinic criteria:

    1. Bone marrow plasma cells between 10% and 60%
    2. Serum M-protein ≥ 3 g/dL [except IgA ≥ 2 g/dL] or urine M-protein > 500 mg per 24 hours
    3. Serum free light chain ratio < 0.126 or > 8; an involved to uninvolved ratio of ≥ 100 is permitted
    4. 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
  2. Diagnosed with SMM within the last 4 years

Laboratory

  1. 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).
  2. 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)
  3. PT/INR < 1.5 x ULN and PTT (aPTT) < 1.5 x ULN

    Demographic

  4. Men and women ≥ 18 years of age
  5. Eastern Cooperative Oncology Group (ECOG) performance status of < 2

Exclusion Criteria Disease-Related

  1. No end organ damage attributable to a plasma cell disorder, defined as having ANY of the following:

    1. Hypercalcemia: Serum calcium > 1 mg/dL above the upper limit of normal or > 11 mg/dL
    2. Renal insufficiency: Serum creatinine > 2 mg/dL or creatinine clearance < 30 mL per min
    3. Anemia: Hemoglobin value > 2 g/dL below the upper limit of normal or a hemoglobin value < 10 g/dL
    4. Bone lesions: One or more lytic lesions on skeletal radiography, CT, MRI, PET-CT, or PET-MRI
  2. Bone marrow plasma cells < 10% or > 60%
  3. Has received prior anti-myeloma therapy of any type
  4. Has received prior bisphosphonate therapy
  5. 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
  6. Osteoporosis, defined as having a T-score on DEXA of ≤ -2.5

Concurrent Conditions

  1. 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
  2. Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc). Any use of corticosteroids EITHER for > 14 days OR at dosages > 20 mg/day of prednisone or equivalent is prohibited.
  3. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
  4. Recent infection requiring systemic treatment that was completed ≤ 14 days before the first dose of study drug
  5. Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
  6. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  7. Known HIV, HCV or HBV infection. Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
  8. Any uncontrolled active systemic infection
  9. Major surgery within 4 weeks of first dose of study drug
  10. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigators' opinion, could compromise the subject's safety or put the study outcomes at undue risk
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lisa La, MS 212-241-7873 lisa.la@mssm.edu
Contact: Ajai Chari, MD 212-241-7873 ajai.chari@mountsinai.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02943473
Other Study ID Numbers  ICMJE GCO 16-1867
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ajai Chari, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Collaborators  ICMJE Pharmacyclics LLC.
Investigators  ICMJE
Principal Investigator: Ajai Chari, MD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP