Multiple MyelomaPhase 1/2NCT02206425
Ixazomib as a Replacement for Carfilzomib and Bortezomib for Multiple Myeloma Patients
A Phase 1/2 study testing Melphalan, Prednisone and Cyclophosphamide in people with Multiple Myeloma, run by Oncotherapeutics at 12 sites in United States.
Trial summary
The goal of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of ixazomib given as part of a combination therapy to treat subjects with relapsed (subjects whose disease came back) or refractory (subjects whose disease did not respond to past treatment) multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Melphalan, Prednisone and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 12 sitesUnited States
- Study dates
- Sep 2014to 6 Mar 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients 18 years or older
- Patients must have a diagnosis of MM, based on standard criteria as follows:
- Major criteria:
- plasmacytomas on tissue biopsy
- bone marrow plasmacytosis (greater than 30% plasma cells)
- monoclonal immunoglobulin spike on serum electrophoresis IgG greater than 3.5 g/dL or IgA greater than 2.0 g/dL; kappa or lambda light chain excretion greater than 1 g/day on 24 hour urine protein electrophoresis
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- Minor criteria:
- bone marrow plasmacytosis (10% to 30% plasma cells)
- monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
- lytic bone lesions
- normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600 mg/dL
- Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:
- any 2 of the major criteria
- major criterion 1 plus minor criterion 2, 3, or 4
- major criterion 3 plus minor criterion 1 or 3
- minor criteria 1, 2, and 3, or 1, 2, and 4
- Currently has progressive MM that has previously progressed or is currently progressing while receiving or within 8 weeks of receiving bortezomib or carfilzomib as part of a combination treatment. MM patients that demonstrate refractory disease, as defined below, are both eligible for enrollment provided they fulfill the other eligibility criteria:
- Patients are refractory to a bortezomib or carfilzomib combination regimen, when they progress while currently receiving a bortezomib or carfilzomib combination treatment, or within 8 weeks of its last dose. Patients are considered relapsed, when they progress between 8 and 12-weeks from their last dose of bortezomib or carfilzomib as part of a bortezomib or carfilzomib combination therapy. Prior treatment with four days or less of a total of 400 mg of prednisone (or an equivalent potency of another steroid) for MM will not be considered a regimen.
- Patients that were on bortezomib-containing regimens must have been administered at least 4 doses of a minimum of 1.0 mg/m2 in no more than 28-days cycles. Subjects must have received at least one cycle meeting this definition and have shown PD to be considered eligible
- Patients that were on carfilzomib-containing regimens must have received at least 6 doses of at least 27 mg/m2 in no more than 28 days per cycle. Subjects must have received at least one cycle meeting this definition and have shown PD to be considered eligible
- Progressed from one of the specific bortezomib- or carfilzomib-containing regimens as listed on page 51. Although bortezomib- and carfilzomib-containing combination regimens that are otherwise identical except for the PI result in the same ixazomib regimen, they will be enrolled separately so that safety/efficacy can be separately determined, thereby allowing comparisons based on the prior PI that subjects were exposed to as part of the regimen that they failed (carfilzomib vs. bortezomib)
- Patient may have received a carfilzomib- or bortezomib-containing regimen at any time and may have received other non-proteasome inhibitor-containing intervening treatments
Who cannot join
- Patient has been diagnosed with:
- Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M protein) and skin changes (POEMS) syndrome.3
- Primary amyloidosis
- Plasma cell leukemia
- Severe hypercalcemia, i.e., serum calcium = 12 mg/dL (3.0 mmol/L) corrected for albumin
- Diagnosed or treated for another malignancy within 3 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanomatous skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
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- Impaired cardiac function or clinically significant cardiac diseases, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or multigated acquisition scan (MUGA) evidence of left ventricular ejection fraction (LVEF) below institutional normal within 28 days prior to enrollment, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant
- Patient has peripheral neuropathy grade 3 or higher or Grade 2 with pain on clinical examination during the screening period
- Patient has received the following prior therapy:
- Chemotherapy within 21 days of enrollment (6 weeks for nitrosoureas)
- Corticosteroids (>10 mg/day prednisone or equivalent) within 21 days of enrollment
- Immunotherapy or antibody therapy as well as thalidomide, pomalidomide, lenalidomide, arsenic trioxide, carfilzomib, or bortezomib within 21 days before enrollment
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
- Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Comprehensive Blood and Cancer Center
Bakersfield, California, 93309
John Muir Health Clinical Research Center
Concord, California, 94520
California Cancer Associates for Research & Excellence (cCARE)
Encinitas, California, 92024
Cancer Specialists of North Florida
Fleming Island, Florida, 32003
Robert A. Moss, MD, FACP, Inc
Fountain Valley, California, 92708
cCARE Fresno
Fresno, California, 93720
Hattiesburg Clinic Hematology/Oncology
Hattiesburg, Mississippi, 39401
Oncology Specialists, SC
Niles, Illinois, 60714
Vista Oncology
Olympia, Washington, 98502
Comprehensive Cancer Center at Desert Regional Medical Center
Palm Springs, California, 92262
Lewis Hall Singletary Oncology Center
Thomasville, Georgia, 31792
James Berenson, MD, Inc
West Hollywood, California, 90069
About this study
Official title: A Phase 1/2 Study of Ixazomib as a Replacement for Bortezomib or Carfilzomib for Multiple Myeloma (MM) Patients Recently Relapsed or Refractory to Their Last Combination Regimen Containing Either Bortezomib or Carfilzomib
The goal of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of ixazomib given as part of a combination therapy to treat subjects with relapsed (subjects whose disease came back) or refractory (subjects whose disease did not respond to past treatment) multiple myeloma. More specifically, the study is focused on subjects who were previously treated with bortezomib (Velcade®) or carfilzomib (Kyprolis®) and showed worsening of their myeloma while receiving either one of these drugs in combination therapy. This study is a Phase I/II. Ixazomib is an investigational drug, which means that ixazomib is currently being tested and is not yet approved by the United States Food and Drug Administration (FDA) for subjects with relapsed or refractory multiple myeloma. Ixazomib is a new study drug that belongs to the same class as bortezomib and carfilzomib; however, unlike bortezomib and carfilzomib, ixazomib is taken by mouth. Current studies investigating ixazomib are demonstrating that it is as safe as bortezomib and effective for the treatment of multiple myeloma both on its own and in combination with other multiple myeloma medications, such as lenalidomide and dexamethasone, or prednisone and melphalan.
Read the detailed description
This is a phase 1/2, intra-patient, multicenter, open-label and non-randomized study to evaluate the efficacy and safety of ixazomib as a replacement for bortezomib or carfilzomib among multiple myeloma (MM) patients who have failed proteasome inhibitor (PI)-containing combination regimens. Patients will receive ixazomib once a week in place of bortezomib or carfilzomib in combination with an alkylating agent (melphalan or cyclophosphamide), anthracycline (pegylated doxorubicin [PLD]), immunomodulatory agent (lenalidomide, pomalidomide), ascorbic acid and/or a glucocorticosteroid (dexamethasone, prednisone or methylprednisolone) administered using the same dose(s) and schedule(s) as the last PI-containing regimen that the patients had received and failed. The total number of different prior bortezomib- or carfilzomib-containing regimens that will be evaluated is 10, reflecting those commonly used in the community as follows:
- bortezomib + melphalan + prednisone
- bortezomib + cyclophosphamide + ascorbic acid
- bortezomib + cyclophosphamide + dexamethasone
- bortezomib + PLD + dexamethasone
- bortezomib + dexamethasone
- carfilzomib + dexamethasone
- bortezomib + lenalidomide + dexamethasone
- bortezomib + pomalidomide + dexamethasone
- carfilzomib + lenalidomide + dexamethasone
- carfilzomib + pomalidomide + dexamethasone
This study will enroll 60 patients who are refractory to a bortezomib- or carfilzomib-containing combination regimen, as demonstrated by progressive disease (PD) while being treated, or who have relapsed within 8 weeks from the last dose of bortezomib or carfilzomib in their last PI-containing combination regimen.
Ixazomib will replace bortezomib or carfilzomib using the same PI-containing regimen the patients failed.The study will consist of: 1) a screening period; 2) up to eight 28-day treatment cycles; 3) a maintenance period; 4) a final assessment to occur 28 days after the end of the last treatment cycle; and 5) a follow-up period.
Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle to patients enrolled in seven regimens (bortezomib + melphalan + prednisone, bortezomib + dexamethasone, carfilzomib + dexamethasone, bortezomib + lenalidomide + dexamethasone, bortezomib + pomalidomide + dexamethasone, carfilzomib + lenalidomide + dexamethasone, carfilzomib + pomalidomide + dexamethasone). Subjects on those regimens receiving 4 mg of ixazomib from the beginning of the trial will continue to do so for the length of the study, unless they suffer from adverse events requiring dose reductions. For the other three regimens, bortezomib + cyclophosphamide + dexamethasone, bortezomib + cyclophosphamide + ascorbic acid, and bortezomib + PLD + dexamethasone, the MTD for ixazomib is unknown and intra-patient dose escalation will be performed to determine the specific MTD for each of them. For these three regimens, ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed.
- Conditions
- Multiple Myeloma
- Being tested
- Melphalan, Prednisone, Cyclophosphamide, Dexamethasone, Ascorbic acid
- Keywords
- multiple myeloma, Relapsed/refractory, Ixazomib, Proteasome inhibitor, Oral
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelphalanDrug
Also called Phenylalanine mustard, Alkeran
Melphalan will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
PrednisoneDrug
Also called Cortan, Deltasone, Orasone, Prednisone Intensol
Prednisone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
CyclophosphamideDrug
Also called Cytoxan, CPM, CTX, CYT
Cyclophosphamide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
DexamethasoneDrug
Also called Decadron, Dexamethasone Intensol, Dexpak Taperpak
Dexamethasone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
Ascorbic acidDietary supplement
Also called Vitamin C
Vitamin C will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
PLDDrug
Also called ATI-0918, doxorubicin hydrochloride liposome, doxorubicin hydrochloride liposome injection, liposomal adriamycin
Pegylated liposomal doxorubicin will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
LenalidomideDrug
Also called Revlimid
Lenalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
PomalidomideDrug
Also called Pomalyst
Pomalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
| Study group | Role | What they receive |
|---|---|---|
| bortezomib + melphalan + prednisone | Experimental | Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Receives: Drug: Melphalan; Drug: Prednisone |
| bortezomib + dexamethasone | Experimental | Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Receives: Drug: Dexamethasone |
| carfilzomib + dexamethasone | Experimental | Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Receives: Drug: Dexamethasone |
| bortezomib + lenalidomide + dexamethasone | Experimental | Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Receives: Drug: Dexamethasone; Drug: Lenalidomide |
| carfilzomib + lenalidomide + dexamethasone | Experimental | Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Receives: Drug: Dexamethasone; Drug: Lenalidomide |
| bortezomib + cyclophosphamide + dexamethasone | Experimental | MTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Receives: Drug: Cyclophosphamide; Drug: Dexamethasone |
| bortezomib + cyclophosphamide + ascorbic acid | Experimental | MTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Due to a potential drug-drug interaction between ixazomib and ascorbic acid, patients will receive ixazomib in the clinic in the morning and will be instructed to take ascorbic acid in the evening, followed by cyclophosphamide. Receives: Drug: Cyclophosphamide; Dietary Supplement: Ascorbic acid |
| bortezomib + PLD + dexamethasone | Experimental | MTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Receives: Drug: Dexamethasone; Drug: PLD |
| bortezomib + pomalidomide + dexamethasone | Experimental | Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Receives: Drug: Dexamethasone; Drug: Pomalidomide |
| carfilzomib + pomalidomide + dexamethasone | Experimental | Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Receives: Drug: Dexamethasone; Drug: Pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) for selected regimens
MTD determined via the number of dose-limiting toxicities (DLTs) per cohort for the following ixazomib- containing combinations:
bortezomib+ cyclophosphamide + dexamethasone, bortezomib + cyclophosphamide + ascorbic acid, bortezomib + PLD + dexamethasone
Measured: Cycles 1-2 for selected regimens (up to 2 months)
Number of subjects with adverse events
Occurrence of adverse events throughout the study, graded via CTCAE v 4.03 criteria
Measured: up to 48 months
Overall response rate (ORR)
Complete response (CR)+ very good partial response (VGPR) + partial response (PR), defined using IMWG criteria
Measured: up to 48 months
Clinical benefit rate (CBR)
CBR=ORR + minor response (MR)
Measured: up to 48 months
Secondary outcomes (6)
Time to Progression
Time from initiation of therapy to progressive disease
Measured: at least over 48 months
Progression-free survival (PFS)
Time from initiation of therapy to progressive disease or death from any cause, whichever occurs first
Measured: at least over 48 months
Time to response (TTR)
Time from the initiation of therapy to the first evidence of a confirmed response
Measured: up to 48 months
Duration of response (DOR)
Time from the first response (> PR) to progressive disease
Measured: at least over 48 months
Overall survival (OS)
Time from initiation of therapy to death from any cause or last follow-up visit
Measured: at least over 48 months
Peripheral Neuropathy (PN)
Incidence and severity among patients receiving ixazomib compared to their baseline PN when they entered the trial, defined by CTCAE v4.0.3 and FACT-GOG/NTX questionnaire score.
Measured: up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2014 (estimated)
- Study startSep 2014
- Primary completion19 Jan 2018
- Study completion6 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda
- Responsible party
- Sponsor
- Investigators
- James R Berenson, MD, Principal investigator, James R. Berenson MD, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02206425
- Sponsor's protocol ID
- X16041
- Other IDs
- IISR-2013-M100118
- Status last verified
- Oct 2023
- First submitted
- 30 Jul 2014
- Last updated
- 31 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of Ixazomib as a Replacement for Bortezomib or Carfilzomib for Multiple Myeloma (MM) Patients Recently Relapsed or Refractory to Their Last Combination Regimen Containing Either Bortezomib or Carfilzomib
- ClinicalTrials.gov ID
- NCT02206425
- Acronym / sponsor ID
- X16041
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, Relapsed/refractory, Ixazomib, Proteasome inhibitor, Oral
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- OncotherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Takeda
- Study start
- Sep 2014 (actual)
- Primary completion
- 19 Jan 2018 (actual)
- Study completion
- 6 Mar 2018 (actual)
- First posted
- 1 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of ixazomib given as part of a combination therapy to treat subjects with relapsed (subjects whose disease came back) or refractory (subjects whose disease did not respond to past treatment) multiple myeloma. More specifically, the study is focused on subjects who were previously treated with bortezomib (Velcade®) or carfilzomib (Kyprolis®) and showed worsening of their myeloma while receiving either one of these drugs in combination therapy. This study is a Phase I/II. Ixazomib is an investigational drug, which means that ixazomib is currently being tested and is not yet approved by the United States Food and Drug Administration (FDA) for subjects with relapsed or refractory multiple myeloma. Ixazomib is a new study drug that belongs to the same class as bortezomib and carfilzomib; however, unlike bortezomib and carfilzomib, ixazomib is taken by mouth. Current studies investigating ixazomib are demonstrating that it is as safe as bortezomib and effective for the treatment of multiple myeloma both on its own and in combination with other multiple myeloma medications, such as lenalidomide and dexamethasone, or prednisone and melphalan.
Detailed description
This is a phase 1/2, intra-patient, multicenter, open-label and non-randomized study to evaluate the efficacy and safety of ixazomib as a replacement for bortezomib or carfilzomib among multiple myeloma (MM) patients who have failed proteasome inhibitor (PI)-containing combination regimens. Patients will receive ixazomib once a week in place of bortezomib or carfilzomib in combination with an alkylating agent (melphalan or cyclophosphamide), anthracycline (pegylated doxorubicin [PLD]), immunomodulatory agent (lenalidomide, pomalidomide), ascorbic acid and/or a glucocorticosteroid (dexamethasone, prednisone or methylprednisolone) administered using the same dose(s) and schedule(s) as the last PI-containing regimen that the patients had received and failed. The total number of different prior bortezomib- or carfilzomib-containing regimens that will be evaluated is 10, reflecting those commonly used in the community as follows:
- bortezomib + melphalan + prednisone
- bortezomib + cyclophosphamide + ascorbic acid
- bortezomib + cyclophosphamide + dexamethasone
- bortezomib + PLD + dexamethasone
- bortezomib + dexamethasone
- carfilzomib + dexamethasone
- bortezomib + lenalidomide + dexamethasone
- bortezomib + pomalidomide + dexamethasone
- carfilzomib + lenalidomide + dexamethasone
- carfilzomib + pomalidomide + dexamethasone
This study will enroll 60 patients who are refractory to a bortezomib- or carfilzomib-containing combination regimen, as demonstrated by progressive disease (PD) while being treated, or who have relapsed within 8 weeks from the last dose of bortezomib or carfilzomib in their last PI-containing combination regimen.
Ixazomib will replace bortezomib or carfilzomib using the same PI-containing regimen the patients failed.The study will consist of: 1) a screening period; 2) up to eight 28-day treatment cycles; 3) a maintenance period; 4) a final assessment to occur 28 days after the end of the last treatment cycle; and 5) a follow-up period.
Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle to patients enrolled in seven regimens (bortezomib + melphalan + prednisone, bortezomib + dexamethasone, carfilzomib + dexamethasone, bortezomib + lenalidomide + dexamethasone, bortezomib + pomalidomide + dexamethasone, carfilzomib + lenalidomide + dexamethasone, carfilzomib + pomalidomide + dexamethasone). Subjects on those regimens receiving 4 mg of ixazomib from the beginning of the trial will continue to do so for the length of the study, unless they suffer from adverse events requiring dose reductions. For the other three regimens, bortezomib + cyclophosphamide + dexamethasone, bortezomib + cyclophosphamide + ascorbic acid, and bortezomib + PLD + dexamethasone, the MTD for ixazomib is unknown and intra-patient dose escalation will be performed to determine the specific MTD for each of them. For these three regimens, ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| bortezomib + melphalan + prednisone | Experimental | Drug: Melphalan, Drug: PrednisoneIxazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. |
| bortezomib + dexamethasone | Experimental | Drug: DexamethasoneIxazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. |
| carfilzomib + dexamethasone | Experimental | Drug: DexamethasoneIxazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. |
| bortezomib + lenalidomide + dexamethasone | Experimental | Drug: Dexamethasone, Drug: LenalidomideIxazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. |
| carfilzomib + lenalidomide + dexamethasone | Experimental | Drug: Dexamethasone, Drug: LenalidomideIxazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. |
| bortezomib + cyclophosphamide + dexamethasone | Experimental | Drug: Cyclophosphamide, Drug: DexamethasoneMTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. |
| bortezomib + cyclophosphamide + ascorbic acid | Experimental | Drug: Cyclophosphamide, Dietary Supplement: Ascorbic acidMTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. Due to a potential drug-drug interaction between ixazomib and ascorbic acid, patients will receive ixazomib in the clinic in the morning and will be instructed to take ascorbic acid in the evening, followed by cyclophosphamide. |
| bortezomib + PLD + dexamethasone | Experimental | Drug: Dexamethasone, Drug: PLDMTD determination. Ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. |
| bortezomib + pomalidomide + dexamethasone | Experimental | Drug: Dexamethasone, Drug: PomalidomideIxazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. |
| carfilzomib + pomalidomide + dexamethasone | Experimental | Drug: Dexamethasone, Drug: PomalidomideIxazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed. Patients that were on a 21-day cycle schedule will follow a 28-day cycle schedule and receive ixazomib on days 1, 8 and 15. Other drugs will be administered on the same days as they were given on their prior 21-day cycle schedule, except that, in the new 28-day schedule, day 1 of other drugs will be the same as day 1 of ixazomib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Male or female patients 18 years or older
- Patients must have a diagnosis of MM, based on standard criteria as follows:
- Currently has progressive MM that has previously progressed or is currently progressing while receiving or within 8 weeks of receiving bortezomib or carfilzomib as part of a combination treatment. MM patients that demonstrate refractory disease, as defined below, are both eligible for enrollment provided they fulfill the other eligibility criteria:
- Patients that were on bortezomib-containing regimens must have been administered at least 4 doses of a minimum of 1.0 mg/m2 in no more than 28-days cycles. Subjects must have received at least one cycle meeting this definition and have shown PD to be considered eligible
- Patients that were on carfilzomib-containing regimens must have received at least 6 doses of at least 27 mg/m2 in no more than 28 days per cycle. Subjects must have received at least one cycle meeting this definition and have shown PD to be considered eligible
Key exclusion criteria (14 listed)
- Patient has been diagnosed with:
- Diagnosed or treated for another malignancy within 3 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanomatous skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Impaired cardiac function or clinically significant cardiac diseases, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or multigated acquisition scan (MUGA) evidence of left ventricular ejection fraction (LVEF) below institutional normal within 28 days prior to enrollment, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant
- Patient has peripheral neuropathy grade 3 or higher or Grade 2 with pain on clinical examination during the screening period
- Patient has received the following prior therapy:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelphalanAlso: Phenylalanine mustard, AlkeranMelphalan will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient). | Drug | bortezomib + melphalan + prednisone |
| PrednisoneAlso: Cortan, Deltasone, Orasone, Prednisone IntensolPrednisone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient). | Drug | bortezomib + melphalan + prednisone |
| CyclophosphamideAlso: Cytoxan, CPM, CTX, CYTCyclophosphamide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient). | Drug | bortezomib + cyclophosphamide + ascorbic acid, bortezomib + cyclophosphamide + dexamethasone |
| DexamethasoneAlso: Decadron, Dexamethasone Intensol, Dexpak TaperpakDexamethasone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient). | Drug | bortezomib + PLD + dexamethasone, bortezomib + cyclophosphamide + dexamethasone, bortezomib + dexamethasone, bortezomib + lenalidomide + dexamethasone, bortezomib + pomalidomide + dexamethasone, carfilzomib + dexamethasone, carfilzomib + lenalidomide + dexamethasone, carfilzomib + pomalidomide + dexamethasone |
| Ascorbic acidAlso: Vitamin CVitamin C will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient). | Dietary supplement | bortezomib + cyclophosphamide + ascorbic acid |
| PLDAlso: ATI-0918, doxorubicin hydrochloride liposome, doxorubicin hydrochloride liposome injection, liposomal adriamycinPegylated liposomal doxorubicin will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient). | Drug | bortezomib + PLD + dexamethasone |
| LenalidomideAlso: RevlimidLenalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient). | Drug | bortezomib + lenalidomide + dexamethasone, carfilzomib + lenalidomide + dexamethasone |
| PomalidomideAlso: PomalystPomalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient). | Drug | bortezomib + pomalidomide + dexamethasone, carfilzomib + pomalidomide + dexamethasone |
Primary outcome
Maximum tolerated dose (MTD) for selected regimens
Time frame: Cycles 1-2 for selected regimens (up to 2 months)
MTD determined via the number of dose-limiting toxicities (DLTs) per cohort for the following ixazomib- containing combinations: bortezomib+ cyclophosphamide + dexamethasone, bortezomib + cyclophosphamide + ascorbic acid, bortezomib + PLD + dexamethasone
Number of subjects with adverse events
Time frame: up to 48 months
Occurrence of adverse events throughout the study, graded via CTCAE v 4.03 criteria
Overall response rate (ORR)
Time frame: up to 48 months
Complete response (CR)+ very good partial response (VGPR) + partial response (PR), defined using IMWG criteria
Clinical benefit rate (CBR)
Time frame: up to 48 months
CBR=ORR + minor response (MR)
6 secondary outcomes
Time to Progression
Time frame: at least over 48 months
Progression-free survival (PFS)
Time frame: at least over 48 months
Time to response (TTR)
Time frame: up to 48 months
Duration of response (DOR)
Time frame: at least over 48 months
Overall survival (OS)
Time frame: at least over 48 months
Peripheral Neuropathy (PN)
Time frame: up to 48 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James R Berenson, MD principal investigator
James R. Berenson MD, Inc.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Melphalan, Prednisone and Cyclophosphamide in people with Multiple Myeloma, run by Oncotherapeutics at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) for selected regimens (time frame: Cycles 1-2 for selected regimens (up to 2 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2023.