Bone Healing During Ninlaro Exposure

NCT04028115 | Completed Phase 2 DMC

• 1 other identifier: HFE-X 18.01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to investigate if treatment with Ixazomib in multiple myeloma (MM) can strengthen the bones, thus making it resilient to future fractures. Ixazomib will be given at a time point when the disease is in a stable phase, decreasing the likelihood that the potential bone anabolic effect will be abrogated by catabolic effect of active MM. In order to be included in the study, the patient must have treatment demanding MM, and the disease must have been brought into at least partial remission with chemotherapy before inclusion. Moreover, the patient must have pathological bone structure on low dose CT due to the pre-existing disease.

Conditions

Multiple Myeloma

Keywords

WH 540

Outcome Measures

Primary Outcomes (1)

• Healing of osteolytic bone lesions on low dose CT.

  Healing of osteolytic bone lesions on low dose CT. Healing will be evaluated based on the preexisting lesion on low dose CT required upon inclusion. All lesions will be evaluated individually using the inclusion scanning as reference. Healing will be defined as ≥ 25% reduction in the size of osteolytic lesions (a reduction of at least 2 mm in the longest dimension is required), increased sclerosis in the edge of existing lesions, or healing of existing lesions.

  from the inclusion in the protocol until the patient has been in the protocol for 24 months or until the patient leaves the protocol if that happens before 24 months

Secondary Outcomes (9)

• Increased bone formation during Ixazomib treatment in NaF PET.

  3, 12 and 24 months

• Increased bone anabolism during Ixazomib treatment.

  3, 12 and 24 months

• Increased bone formation to bone degradation ratio during Ixazomib treatment.

  3, 12 and 24 months

• Increased bone formation using bone histomorphometric evaluation.

  3, 12 and 24 months

• Changes in the patients' mesenchymal stroma cells toward a more osteoblastic state.

  3, 12 and 24 months

Study Arms (1)

Interventional

EXPERIMENTAL

Patients included in the trial will be treated with Ixazomib 4 mg on day 1, 8, and 15 in a 28-day cycle for up to 24 cycles. In this, study no randomisation will occur. All patients will receive the same treatment.

Drug: Ixazomib

Interventions

Ixazomib DRUG

Scheduled visits: Patients included in the trial will be treated with Ixazomib 4 mg on day 1, 8, and 15 in a 28-day cycle for up to 24 cycles. Patients will be evaluated every 4th week by a medical doctor, prior to initiation of a new cycle of Ixazomib.

Also known as: Ninlaro

Interventional

Eligibility Criteria

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

You may qualify if:

• Symptomatic Multiple Myeloma according to the IMWG criteria.
• Detectable osteolysis on low dose CT (at least 5 mm in size).
• Stable disease, defined as no signs of progressive disease for three months without anti myeloma treatment.
• Achieved, partial response or better, during last line of therapy.
• Signed informed consent.
• Age ≥ 18 years.
• Remaining life expectancy ≥ 6 months.
• ECOG performance status 0-2.
• Female patients who
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, simultaneously, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception).
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following
• Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR

You may not qualify if:

• Treatment with Denosumab within the last 4 weeks.
• Known concurrent malignancy (last five years), excluding skin cancer.
• Known hypersensitivity to Ixazomib.
• Central nervous system involvement.
• Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive Pregnant or lactating women
• Absolute neutrophil count \< 1,000mm3 without growth factor support.
• Alanine aminotransferase \> 3 x upper limit of the normal range.
• Calculated creatinine clearance \< 30 mL/min (using the Cockcroft-Gault equation).
• Total bilirubin \> 1.5 the upper limit of the normal range (ULN).
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, uncontrolled congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort.
• Peripheral neuropathy grade 1 with pain or grade 2.
• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout its.
• Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of Ixazomibzomib including difficulty swallowing.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.

Sponsors & Collaborators

• Thomas Lund: lead

Study Sites (1)

Odense University Hospital

Odense, 5000, Denmark

Location

Related Publications (1)

• Levring MB, Diaz-delCastillo M, Gundesen MT, Cedile O, Andersen CW, Nielsen AL, Moller HEH, Vinholt PJ, Asmussen JT, Kristensen IB, Nyvold CG, Kassem M, Abildgaard N, Andersen TL, Lund T. Ixazomib treatment has a dual effect on bone remodeling in patients with multiple myeloma: follow-up results from a phase 2 clinical study. Bone. 2025 Dec;201:117660. doi: 10.1016/j.bone.2025.117660. Epub 2025 Sep 23.

  PMID: 40998041 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib

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

Study Officials

• Thomas Lund, Ph.D., MD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Pd.D Associate Professor Chief Physician

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 22, 2019
• Study Start: October 24, 2019
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: April 3, 2024

Record last verified: 2024-04

Locations

DK (1)