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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Increased bone formation during Ixazomib treatment in NaF PET. | Increased bone formation during Ixazomib treatment in NaF PET. Increased bone formation will be evaluated in NaF PET by comparing delta values of SUVmax of the individual lesions. The inclusion scan will be used as reference. NaF PET scan will be conducted 45 (+/-5 minutes) minutes after infusion of the NaF tracer. | 3, 12 and 24 months |
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Inclusion Criteria:
Female patients who
Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Lund, Ph.D., MD | Odense University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Odense University Hospital | Odense | 5000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40998041 | Derived | 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. |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| C548400 | ixazomib |
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|
| Increased bone anabolism during Ixazomib treatment. | Increased bone anabolism during Ixazomib treatment. The bone anabolic markers bALP, PINP, and OC will be measured at screening and during treatment. The patient will function as his or her own control, using the bone marker levels at inclusion as reference. | 3, 12 and 24 months |
| Increased bone formation to bone degradation ratio during Ixazomib treatment. | Increased bone formation to bone degradation ratio during Ixazomib treatment. In addition to the anabolic bone markers; the degradation markers CTX and TRAP5b will also be measured. Again using the levels at inclusion, a ratio of bone formation to bone degradation markers will be calculated. Delta values will be calculated during Ixazomib treatment to investigate if bone remodeling changes toward a more anabolic equilibrium. | 3, 12 and 24 months |
| Increased bone formation using bone histomorphometric evaluation. | Increased bone formation using bone histomorphometric evaluation. At inclusion and at predefined selected time points, the patient will have a bone marrow biopsy performed. This biopsy will be stored for later evaluation. Evaluation will be conducted using a slightly modified Masson trichrome staining. | 3, 12 and 24 months |
| Changes in the patients' mesenchymal stroma cells toward a more osteoblastic state. | Changes in the patients' mesenchymal stroma cells toward a more osteoblastic state. At inclusion and after three months, the patients will have a bone marrow biopsy performed. Stromal cells will be harvested, characterized by Cluster of Differentiation markers, methylation changes, global mRNA expression, and grown in culture assays to investigate their osteoblastic potential. | 3, 12 and 24 months |
| Investigate safety and toxicities during Ixazomib treatment. | Investigate safety and toxicities during Ixazomib treatment. Ixazomib has been approved by EMEA in combination with Lenalidomide and Dexamethasone in patients who has relapse of MM after initial therapy. Here, we also wish to give Ixazomib after initial therapy has been completed. However, we wish to give it as monotherapy to patients who do not have active disease. Any toxicity during the study will be registered and graded according to NCI CTCAE version 4 National Cancer Institute Common Terminology Criteria for Adverse Events. (Most recent version can be found at: http://ctep.cancer.gov/protocolDevelopment/electronic\_applications/ctc.htm). | 2 years |
| Depth of cancer response to Ixazomib treatment. | Depth of cancer response to Ixazomib treatment. Ixazomib has an anti-myeloma effect. During the trial, serum and urine M-component as well as serum free light kappa and lambda chains will be measured. Any upgrading of depth of response will be measured in relation to the status prior to the preexisting disease levels before the last treatment was initiated. In addition, changes in disease status during treatment compared to disease burden at inclusion will also be investigated. Bone marrow examination will be done to verify CR. Response is measured according to the International Myeloma Working Group Uniform Response Criteria (2016) appendix 1. | 2 years |
| Adherence to therapy. | Adherence to therapy. Ixazomib will be given for up to 24 cycles or until disease progression (biochemical or symptomatic), see appendix 1 for details, unacceptable toxicities, or withdrawal of consent. In the study we will register time on treatment and reason for discontinuation. As a subpart of this, we will also register time to disease progression during Ixazomib treatment, by calculating from the time when the last treatment was initiated and stopped. | 2 years |
| 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. | 3, 12, and 24 months |
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |