Clinical trial NCT03608501 (phase 2, status: withdrawn)
Conditions: multiple myeloma
ICD codes: C90.01, C90.02, C90.00
Drugs: ixazomib, thalidomide, dexamethasone
SMILES: [H][C@@](CC(C)C)(N=C(O)CN=C(O)C1=C(Cl)C=CC(Cl)=C1)B(O)O, CC(C)NCC(O)COC1=CC=CC2=C1C=CC=C2, C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F
Reason stopped: 
    business decision (no safety or efficacy concerns)
  
Eligibility criteria:

        Inclusion Criteria:

          1. Clonal bone marrow plasma cells >=10% or biopsy-proven bony or extramedullary
             plasmacytoma and any one or more of the following myeloma defining events:

               -  Evidence of end organ damage that can be attributed to the underlying plasma cell
                  proliferative disorder, specifically:

                    -  Hypercalcaemia: serum calcium greater than (>) 1 mg/dL higher than the upper
                       limit of normal (ULN) or >11 mg/dL;

                    -  Renal insufficiency: creatinine clearance <40 milliliter (mL) per minute (as
                       per validated equations) or serum creatinine >2 mg/dL;

                    -  Anemia: haemoglobin value of >20 gram per liter (g/L) below the lower limit
                       of normal, or a haemoglobin value <100 g/L;

                    -  Bone lesions: one or more osteolytic lesions on skeletal radiography,
                       computed tomography (CT), or positron emission tomography (PET)-CT.

               -  Any one or more of the following biomarkers of malignancy:

                    -  Clonal bone marrow plasma cell percentage >=60%.

                    -  Involved: uninvolved serum free light chain ratio >=100.

                    -  Greater than (>) 1 focal lesions on magnetic resonance imaging (MRI)
                       studies. Note: clonality should be established by showing kappa to lambda
                       ratio (κ/λ)-light-chain restriction on flow cytometry, immunohistochemistry,
                       or immunofluorescence. Bone marrow plasma cell percentage should preferably
                       be estimated from a core biopsy specimen; in case of a disparity between the
                       aspirate and core biopsy, the highest value should be used.

          2. Ineligibility to autologous transplantation, as per investigator's discretion,
             regardless of age (the reason for such ineligibility should be recorded on the
             electronic case report form [eCRF]).

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          4. Ability to take concurrent aspirin daily (or enoxaparin subcutaneously daily), per
             published standard or institutional standard of care, as prophylactic anticoagulation.

          5. Note: For participants with prior history of deep vein thrombosis (DVT), low molecular
             weight heparin (LMWH) is mandatory.

          6. Left ventricular ejection fraction (LVEF) >=50%.

          7. Clinical laboratory values as specified below within 7 days before the first dose of
             study drug:

               -  Absolute neutrophil count (ANC) >=1,500 per cubic millimeter (/mm^3), unless
                  related to bone marrow infiltration by malignant plasma cells.

               -  Hemoglobin >=8.0 g/dL

               -  Platelet count >=75,000/mm^3, unless related to bone marrow infiltration by
                  malignant plasma cells (platelet transfusions to help participants meet
                  eligibility criteria are not allowed).

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (AST) less than or
                  equal to (<=) 1.5 times the institutional ULN.

               -  Bilirubin <=1.5 mg/dL (or <=2.5 mg/dL in case of Gilbert-Meulengracht syndrome).

               -  Glomerular filtration rate >=30 milliliter per minute per (mL/min/) 1.73 square
                  meter (m^2) according to the Modification of Diet in Renal Disease (MDRD) study
                  abbreviated formula. If not on target, this evaluation may be repeated once after
                  at least 24 hours.

               -  Prothrombin time (PT) or activated partial thromboplastin time (aPTT) within
                  normal limits.

        Exclusion Criteria:

          1. Presence of non-secretory or oligo-secretory myeloma, smoldering MM, monoclonal
             gammopathy of undetermined significance, plasma-cell leukemia, Waldenstrom's
             macroglobulinemia, primary amyloidosis, or polyneuropathy, organomegaly,
             endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome.

          2. Central nervous system involvement by MM.

          3. Prior radiation therapy involving an estimated >=25% of the hematopoietically active
             bone marrow. Radiotherapy should not be given within 14 days before enrollment. In
             case of palliative radiotherapy for pain control and if the involved field is small, 7
             days will be considered a sufficient interval between the radiation treatment and
             administration of the study drugs.

          4. Treatment with any investigational products within 1 (one) year before the first dose
             of the study drug regimen.

          5. Presence of peripheral neuropathy of grade 1 with pain or grade 2 or higher.

          6. Previous or concurrent history of malignancies other than MM except for curatively
             treated cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder
             cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina
             propria]), or localized prostate cancer.

          7. With evidence or history of bleeding diathesis. Any hemorrhage or bleeding event
             >=common terminology criteria for adverse events (CTCAE) Grade 3 within 4 weeks of
             start of study medication.

          8. Major surgery within 14 days before randomization.

          9. Non-healing wound or ulcer.

         10. Seizure disorder requiring medication.

         11. Systemic treatment with strong cytochrome P-450 3A (CYP3A) inducers (rifampin,
             rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo
             biloba or St. John's wort from Day-14 of cycle 1 until the safety follow-up.

         12. Arterial or venous thrombotic or embolic events such as cerebrovascular accident
             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
             within 3 months before the start of study medication.