Clinical trial NCT04028115: Bone Healing During Ninlaro Exposure
Official title: Bone Healing During Ninlaro Exposure. An Open Label Phase 2 Single Centre Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: WH 540
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2019-07-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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
* 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).

Exclusion Criteria:

* 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.
* Platelet count \< 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before inclusion -Total bilirubin \> 1.5 x the upper limit of the normal range.
* 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).
* Radiotherapy within 14 days before inclusion.
* Major surgery within 14 days before inclusion.
* 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.

Primary outcomes:
measure: Healing of osteolytic bone lesions on low dose CT.
timeFrame: 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:
measure: Increased bone formation during Ixazomib treatment in NaF PET.
timeFrame: 3, 12 and 24 months
measure: Increased bone anabolism during Ixazomib treatment.
timeFrame: 3, 12 and 24 months
measure: Increased bone formation to bone degradation ratio during Ixazomib treatment.
timeFrame: 3, 12 and 24 months
measure: Increased bone formation using bone histomorphometric evaluation.
timeFrame: 3, 12 and 24 months
measure: Changes in the patients' mesenchymal stroma cells toward a more osteoblastic state.
timeFrame: 3, 12 and 24 months
measure: Investigate safety and toxicities during Ixazomib treatment.
timeFrame: 2 years
measure: Depth of cancer response to Ixazomib treatment.
timeFrame: 2 years
measure: Adherence to therapy.
timeFrame: 2 years
measure: Healing of osteolytic bone lesions on low dose CT.
timeFrame: 3, 12, and 24 months
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Odense University Hospital
name: Thomas Lund, Ph.D., MD
role: PRINCIPAL_INVESTIGATOR
References: