Refractory Plasma Cell MyelomaPhase 1/2NCT02119468
Ixazomib Plus Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Relapsed/Refractory Multiple Myeloma
A Phase 1/2 study testing ixazomib citrate, dexamethasone and pomalidomide in people with Refractory Plasma Cell Myeloma and Recurrent Plasma Cell Myeloma, run by City of Hope Medical Center at 5 sites in United States.
Trial summary
This phase I/II trial studies the side effects and best dose of ixazomib and to see how well it works when given together with pomalidomide and dexamethasone in treating patients with relapsed or relapsed/refractory multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Plasma Cell Myeloma, Recurrent Plasma Cell Myeloma
- What is being tested?
- ixazomib citrate, dexamethasone and pomalidomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 5 sitesUnited States
- Study dates
- 30 Jun 2014to 1 Dec 2022
- Phase
- Phase 1/2
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
- Voluntary written informed 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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours of starting pomalidomide or MLN9708 and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide or MLN9708 through 90 days after the last dose of study drug; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 90 days after the last dose of study drug; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
- All patients enrolled into this trial, must be registered in and must comply with all requirements of the POMALYST (pomalidomide) Risk Evaluation and Mitigation Strategy (REMS) program
- Patients must have a diagnosis of relapsed or relapsed and refractory multiple myeloma with a minimum of one prior regimen and a maximum of 5 prior regimens
- Patients must have had therapy with a proteasome inhibitor and lenalidomide and be refractory to lenalidomide according to the International Myeloma Working Group (IMWG) criteria definition of refractory disease (progressive disease on or within 60 days of stopping lenalidomide)
- Patients must have measurable disease defined as one of the following:
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- Serum M protein >= 0.5 g/dL
- Urine M protein >= 200 mg/24 hours
- Serum free light chain >= 10 mg/dL provided the free light chain (FLC) ratio is abnormal
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Platelet count >= 75,000/uL for patients in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count >= 50,000/uL for patients in whom >= 50% of bone marrow nucleated cells are plasma cells; platelet transfusions are not allowed within 3 days of last platelet assessment to confirm eligibility
- Total bilirubin =< 1.5 × the institutional upper limit of the normal range (IULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 × IULN
- Calculated creatinine clearance >= 45 mL/min
Who cannot join
- Female patients who are pregnant or breastfeeding or have a positive serum pregnancy test during the screening period
- Failure to have fully recovered (ie, =< grade 1 toxicity) from the reversible effects of prior chemotherapy
- Prior therapy with a combination regimen containing pomalidomide except the 2 drug combination of pomalidomide and dexamethasone
- Major surgery within 14 days before enrollment
- Radiotherapy within 14 days before enrollment; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the MLN9708
- Central nervous system involvement
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- Infection requiring systemic antibiotic therapy or other serious infection within 14 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 MLN9708, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A (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
- Unable or unwilling to undergo antithrombotic prophylaxis
- 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
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 or pomalidomide including difficulty swallowing
- Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy with 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 on clinical examination during the screening period
- Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial (for all other standard therapies, no treatment within 14 days of the start of this trial)
- Patients who are pomalidomide refractory, defined as patients who progress on or within 60 days of pomalidomide when given as a single agent or with dexamethasone
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322
City of Hope Medical Center
Duarte, California, 91010
Sarah Cannon Research Institute (SCRI)
Nashville, Tennessee, 37203
Mayo Clinic
Rochester, Minnesota, 55905
Mayo Clinic
Scottsdale, Arizona, 85259
About this study
Official title: Phase I/II Trial of MLN9708 Plus Pomalidomide and Dexamethasone for Relapsed or Relapsed Refractory Multiple Myeloma
This phase I/II trial studies the side effects and best dose of ixazomib and to see how well it works when given together with pomalidomide and dexamethasone in treating patients with relapsed or relapsed/refractory multiple myeloma. Ixazomib may stop the growth of cancer by interfering with proteasomes (the protein breakdown mechanism in the cells). Pomalidomide and dexamethasone can modify and regulate the immune system and may stop cancer cells from growing. Giving ixazomib with pomalidomide and dexamethasone may be an effective treatment for relapsed or relapsed/refractory multiple myeloma.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the recommended phase II dose (RP2D) of MLN9708 (ixazomib), when given in combination with pomalidomide and dexamethasone, in patients with relapsed or relapsed/refractory multiple myeloma. (Phase I) II. To estimate the response rate and to evaluate the antitumor activity of the three drug combination: MLN9708 (at the RP2D), pomalidomide and dexamethasone, in patients with relapsed or relapsed/refractory multiple myeloma. (Phase II)
SECONDARY OBJECTIVES:
- To evaluate the safety of MLN9708 at each dose level when given as part of a three drug combination by assessing the following: type, frequency, severity, attribution, time course and duration of adverse events; and clinical laboratory tests at various points in the study. (Phase I) II. To characterize and evaluate toxicities, including type, frequency, severity, attribution, time course and duration, at the RP2D, for the three drug combination. (Phase II) III. To obtain estimates of response duration, depth of response, clinical benefit response, and survival (overall and progression-free), at the RP2D, for the three drug combination. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of ixazomib followed by a phase II study.
Patients receive ixazomib orally (PO) on days 1, 8, and 15; dexamethasone PO on days 1, 8, 15, and 22; and pomalidomide PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years.
- Being tested
- ixazomib citrate, dexamethasone, pomalidomide
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ixazomib citrateDrug
Also called MLN9708, proteasome inhibitor MLN9708
Given orally
dexamethasoneDrug
Also called Aeroseb-Dex, Decaderm, Decadron, DM
Given orally
pomalidomideDrug
Also called CC-4047, Pomalyst
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (3mg MLN9708) | Experimental | Patients receive 3mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: ixazomib citrate; Drug: dexamethasone; Drug: pomalidomide |
| Treatment (4mg MLN9708) | Experimental | Patients receive 4mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: ixazomib citrate; Drug: dexamethasone; Drug: pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Dose-Limiting Toxicities (Phase I)
Dose Limiting Toxicity (DLT) is defined as any of the toxicities in Section 7.3 that are at least possibly related to either Pomalidomide or MLN9708 that occur during cycle 1. Toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03. The highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in course 1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I.
Measured: From the initial treatment to Day 28 (Cycle #1)
Overall Response Rate at the Recommended Phase II Dose (RP2D)
Over response rate is calculated as the percent of evaluable patients that have confirmed stringent complete remission (sCR), complete remission (CR), very good partial remission (VGPR) or partial remission [PR]) per modified IMWG criteria. sCR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow. CR defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR defined as serum and urine M-protein detectable or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR defined as > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h. The exact 95% confidence intervals are calculated for the estimate.
Measured: From the initial treatment to 24 months
Maximum Tolerated Dose (MTD) of MLN9708 (Phase I)
The highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in Cycle #1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I.
Measured: From the initial treatment to Day 28 (Cycle #1)
Secondary outcomes (4)
Duration of Response at the Recommended Phase II Dose (RP2D)
Time from the date of first documented response (sCR/CR/VGPR or PR) to documented disease relapse, progression or death whichever occurs first. sCR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow. CR defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR defined as serum and urine M-protein detectable or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR defined as > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h.
Measured: Time interval from the date of first documented response (sCR/CR/VGPR or PR) to documented disease relapse, progression or death whichever occurs first, up to 24 months
Clinical Benefit Response Rate at the Recommended Phase II Dose (RP2D)
Clinical benefit response rate is calculated as the percent of evaluable patients that have confirmed stringent complete remission (sCR), complete remission (CR), very good partial remission (VGPR), partial remission (PR), minimal response (MR) or stable disease (SD) per modified IMWG criteria. The exact 95% confidence intervals are calculated for the estimate.
Measured: From the initial treatment up to 24 months
One-Year Overall Survival at the Recommended Phase II Dose (RP2D)
Overall survival (OS) was measured from initial treatment to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula.
Measured: Date of first dose of study drug to date of death from any cause, up to 24 months. And the median follow-up for the surviving patients is at least one year.
One-Year Progression-Free Survival at the Recommend Phase II Dose (RP2D)
Progression-free survival (PFS) was defined as time from initial treatment to recurrence, progression or death. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works. Progression-free survival was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula [Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.]
Measured: Date of first dose of study drug to first documented disease relapse, progression or death from any cause, whichever occurs first, up to 24 months. And the median follow-up for the surviving patients is at least one year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study start30 Jun 2014
- Primary completion18 May 2016
- Study completion1 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Refractory Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- 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
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Amrita Krishnan, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02119468
- Sponsor's protocol ID
- 12267
- Other IDs
- NCI-2014-00803, 12267
- Status last verified
- Mar 2024
- First submitted
- 17 Apr 2014
- Last updated
- 15 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes