Multiple Myeloma
Conditions
Brief summary
The goal of this proposal is to develop a more effective and better tolerated regimen. Ixazomib appears to have greater activity than bortezomib with less peripheral neuropathy.
Detailed description
1.1 PRIMARY OBJECTIVE: 1.1.1 To evaluate the response rate of Ixazomib with metronomic cyclophosphamide and dexamethasone for first-line treatment of multiple myeloma 1.2 SECONDARY OBJECTIVES: 1.2.1To evaluate the toxicities associated with Ixazomib with metronomic cyclophosphamide and dexamethasone. 1.2.2 Estimate the progression-free survival and overall survival of Ixazomib with metronomic cyclophosphamide and dexamethasone for first-line treatment of multiple myeloma
Interventions
DRUGIxazomib
Cycle 1: Ixazomib: 4mg/day 1, 8, 15 Cycles 2-6: Ixazomib: 4mg/day 1, 4, 8, 11, 15, 18, Maintenance: Ixazomib at 4 mg days 1, 8 and 15 of a 28 day cycle for 1 ½ years
DRUGCyclophosphamide
Cycle 1: Cyclophosphamide: 50 mg/day continuous daily Cycles 2-6: Cyclophosphamide: 50 mg/day continuous daily
DRUGDexamethasone
Cycle 1: Dexamethasone: 20 mg/day 1, 8, 15 Cycles 2-6: Dexamethasone: 20 mg/day 1, 4, 8, 11, 15, 18
Sponsors
Rhode Island Hospital
The Miriam Hospital
Memorial Hospital of Rhode Island
John L. Reagan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years of age * Histologically confirmed multiple myeloma according to WHO classification. Pathology report to be sent to BrUOG for confirmation * Diagnosis of Multiple Myeloma that has not been previously treated (although patients that received emergent steroid and/or local radiation therapy will be permitted to enter the study). , Details need to be submitted to BrUOG with dates and doses. * Measureable disease defined as either an elevated serum M-protein, urine M-protein, bone marrow involvement \>30% or serum free light chains per the IMWG criteria. Confirmation to be sent to BrUOG, see section 7 for criteria * Life expectancy of ≥ 6 months, confirmation per treating investigator required * Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. If transfusional support provided, please document for submission to BrUOG * Calculated creatinine clearance ≥30 mL/min (based on the Cockcroft-Gault Equation below) For males: Creatinine Clearance = (140-age\[years\] x weight \[kg\]) 72 x (serum creatinine\[mg/dL\]) For females: Creatinine Clearance = 0.85 (140-age\[years\] x weight \[kg\]) 72 x (serum creatinine\[mg/dL\]) * ECOG performance status of 0-1. * Adequate Liver function; AST or ALT \< 3.0 x upper limit of normal (ULN); Total bilirubin \<1.5x ULN * Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. * 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, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug and obtain a pregnancy test, which must come back negative prior to drug, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject and obtain a serum pregnancy test, which must come back negative prior to drug. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.) Documentation and confirmation of conversations and patient commitment to contraception is required to be noted and sent to BrUOG. Female's menopausal status to be documented and submitted to BrUOG if applicable. Pregnancy test, if applicable, required to be sent to BrUOG. * Male patients, even if surgically sterilized (ie, 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.) Documentation and confirmation of conversations and patient commitment to contraception is required to be noted and sent to BrUOG.
Exclusion criteria
* Female patients who are lactating or have a positive serum pregnancy test during the screening period. * Any surgery within 14 days before enrollment. * Radiotherapy within 14 days before enrollment. * Central nervous system involvement (myeloma-related). * Active infection requiring systemic antibiotic therapy or other serious active infection within 7 days before study enrollment. * Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. * Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort. * Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. * Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. If not applicable, then investigator to document not applicable * Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. If not applicable, then investigator to document not applicable * Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing. If not applicable, then investigator to document not applicable * Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. * Patient has ≥ Grade 2 peripheral neuropathy or Grade 1 with pain. * Participation in other therapeutic clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluation of the Response Rate of Ixazomib With Metronomic Cyclophosphamide and Dexamethasone for First-line Treatment of Multiple Myeloma. | Through study treatment completion, an average of 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of the Toxicities Associated With Ixazomib With Metronomic Cyclophosphamide and Dexamethasone. | Assessed at baseline and end of study, up to 2 years, end of study reported |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ixazomib Regimen Cycle 1: Ixazomib: 4mg/day 1, 8, 15, Cyclophosphamide: 50 mg/day continuous daily, Dexamethasone: 20 mg/day 1, 8, 15 Cycles 2-6: Ixazomib: 4mg/day 1, 4, 8, 11, 15, 18, Cyclophosphamide: 50 mg/day continuous, daily, Dexamethasone: 20 mg/day 1, 4, 8, 11, 15, 18
Maintenance:
Ixazomib at 4 mg days 1, 8 and 15 of a 28 day cycle for 1 ½ years
Ixazomib: Cycle 1:
Ixazomib: 4mg/day 1, 8, 15
Cycles 2-6:
Ixazomib: 4mg/day 1, 4, 8, 11, 15, 18,
Maintenance:
Ixazomib at 4 mg days 1, 8 and 15 of a 28 day cycle for 1 ½ years
Cyclophosphamide: Cycle 1:
Cyclophosphamide: 50 mg/day continuous daily
Cycles 2-6:
Cyclophosphamide: 50 mg/day continuous daily
Dexamethasone: Cycle 1:
Dexamethasone: 20 mg/day 1, 8, 15
Cycles 2-6:
Dexamethasone: 20 mg/day 1, 4, 8, 11, 15, 18 | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Ixazomib Regimen | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 4 Participants | — |
| Age, Categorical Between 18 and 65 years | 8 Participants | — |
| Age, Continuous | 61 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 12 Participants | — |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 10 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 1 / 12 |
Outcome results
Primary
Evaluation of the Response Rate of Ixazomib With Metronomic Cyclophosphamide and Dexamethasone for First-line Treatment of Multiple Myeloma.
Time frame: Through study treatment completion, an average of 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ixazomib Regimen | Evaluation of the Response Rate of Ixazomib With Metronomic Cyclophosphamide and Dexamethasone for First-line Treatment of Multiple Myeloma. | 12 Participants |
Secondary
Evaluation of the Toxicities Associated With Ixazomib With Metronomic Cyclophosphamide and Dexamethasone.
Time frame: Assessed at baseline and end of study, up to 2 years, end of study reported
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ixazomib Regimen | Evaluation of the Toxicities Associated With Ixazomib With Metronomic Cyclophosphamide and Dexamethasone. | 12 Participants |