Multiple MyelomaPhase 2NCT02294357
Weekly 70 mg/m2 Carfilzomib for Multiple Myeloma Patients Refractory to 27 mg/m2 Carfilzomib
A Phase 2 study testing Carfilzomib, Dexamethasone and Prednisone in people with Multiple Myeloma, run by Oncotherapeutics at 7 sites in United States.
Trial summary
The purpose of this Phase II study is to evaluate the safety and effectiveness (good and bad effects) of carfilzomib given as a 30-minute infusion and at a dose of 70 mg/m2 to treat patients with multiple myeloma (MM), who are currently showing progressive disease (worsening) and had progressed (did not respond to… 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?
- Carfilzomib, Dexamethasone and Prednisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 7 sitesUnited States
- Study dates
- Dec 2014to 22 Sep 2020
- Phase
- Phase 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
- Has 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 (Ig) 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.
- Minor criteria:
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- 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
- Patient must meet one of the following:
- Currently, patient has progressive MM that has progressed while receiving twice weekly carfilzomib 27mg/m2 alone or as part of their last carfilzomib-containing combination regimen
- Currently, the patient is not in CR and plateaued (as defined by unchanged disease markers for at least 8 weeks) while treated with carfilzomib (twice weekly 27 mg/m2) and dexamethasone with or without lenalidomide or pomalidomide
- Patients who were previously receiving a carfilzomib (twice weekly 27 mg/m2) containing regimen and are currently receiving carfilzomib (twice weekly 27mg/m2) and dexamethasone maintenance therapy with or without lenalidomide or pomalidomide and are not in CR and have plateaued
- Patient must have received at least one full cycle of carfilzomib at a dose of twice weekly 27mg/m2 prior to showing evidence of PD or plateauing from their last carfilzomib-containing regimen.
- Patient must have previously received treatment with an immunomodulatory agents lenalidomide or pomalidomide to be eligible for the study (applicable only for subjects who qualify via inclusion criteria 2B or 2C).
- There is no limit to the number of prior lines of therapy that a patient may have received.
- Measurable disease, as defined by one or more of the following (assessed within 14 days prior to first dose):
- Serum M-protein ≥ 0.5 g/dL, or
- Urine M-protein ≥ 200 mg/24 hours, or
- Only in patients who do not meet a or b, then use serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal κ/λ ratio
- Age ≥ 18 years.
- Life expectancy ≥ 6 months.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Adequate hepatic function within 14 days prior to first dose, with bilirubin < 1.5 × the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 × ULN.
- LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
- Absolute neutrophil count (ANC) ≥ 1000/mm3 within 14 days prior to first dose. Screening ANC is to be independent of granulocyte colony stimulating factor support for ≥ 1 week and pegylated granulocyte colony stimulating factor for ≥ 2 weeks.
- Hemoglobin ≥ 8.0 g/dL within 14 days prior to enrollment. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion must have been at least 7 days prior to obtaining screening hemoglobin.
- Platelet count ≥ 75,000/mm3 (≥ 50,000/mm3 if myeloma involvement in the bone marrow is > 50%) within 14 days prior to first dose. Patients must not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count.
- Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min within 14 days prior to first dose. Calculations are based on a standard formula, such as the Cockcroft and Gault: [(140 - Age) × Mass (kg) / (72 × Creatinine mg/ dL)]; multiply result by 0.85 if female.
- Written informed consent in accordance with federal, local, and institutional guidelines.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within the 7 days prior to study drug administration and a negative urine pregnancy test within the 3 days prior to the first study drug administration
- WOCBP and male subjects who are sexually active with WOCBP must agree to use 2 highly effective methods of contraception during the study and for 30 days following the last dose of study treatment including a male condom.
Who cannot join
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential)
- Waldenström's macroglobulinemia
- Amyloidosis
- Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to first dose
- Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to first dose
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- Treatment with bortezomib (Velcade®), thalidomide, pomalidomide (Pomalyst®) or lenalidomide (Revlimid®) within 21 days prior to first dose
- Focal radiation therapy within 7 days prior to first dose. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (i.e., prior radiation must have been to < 30% of the bone marrow)
- Immunotherapy within 21 days prior to first dose
- Major surgery within 21 days prior to first dose
- Active congestive heart failure (New York Heart Association [NYHA] Classes III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to first dose. Echocardiogram or MUGA evidence of left ventricular ejection fraction (LVEF) below institutional normal within 28 days prior to enrollment
- Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at HBV), or antifungal agents within 14 days prior to first dose
- Known human immunodeficiency virus (HIV) seropositivity
- Known active hepatitis B or C virus infection (except for patients with HBV receiving and responding to HBV antiviral therapy: these patients are allowed)
- Patients with known cirrhosis
- Second malignancy within the past 3 years, except:
- Adequately treated basal cell or squamous cell skin cancer
- Carcinoma in situ of the cervix
- Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
- Breast carcinoma in situ with full surgical resection
- Treated medullary or papillary thyroid cancer
- Patients with myelodysplastic syndrome
- Significant neuropathy (Grades 3 to 4) within 14 days prior to first dose
- Peripheral neuropathy with pain ≥ G2 within 14 days prior to first dose
- Patients with baseline hepatic impairment
- Women who are pregnant and/or breast feeding
- Known hypersensitivity to dexamethasone
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
- Hypersensitivity to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs.
- Prior participation in any Onyx-sponsored Phase 3 trial
- Ongoing graft-versus-host disease
- Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
- Any other clinically significant medical disease or psychiatric condition that, in the Investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Gabrail Cancer Center
Canton, Ohio, 44718
California Cancer Associates for Research & Excellence (cCARE)
Encinitas, California, 92024
Cancer Specialists of North Florida
Fleming Island, Florida, 32003
Hudson Valley Hem/Onc Associates
Poughkeepsie, New York, 12601
Blood & Cancer Center of East Texas
Tyler, Texas, 75701
Wellness Oncology and Hematology
West Hills, California, 91307
James R Berenson, MD, Inc.
West Hollywood, California, 90069
About this study
Official title: A Phase 2 Study of Weekly 70 mg/m2 Carfilzomib for Multiple Myeloma Patients Refractory to 27 mg/m2 Carfilzomib
The purpose of this Phase II study is to evaluate the safety and effectiveness (good and bad effects) of carfilzomib given as a 30-minute infusion and at a dose of 70 mg/m2 to treat patients with multiple myeloma (MM), who are currently showing progressive disease (worsening) and had progressed (did not respond to treatment) within 8 weeks of receiving treatment with twice weekly 27mg/m2 of carfilzomib. Carfilzomib is approved by the U.S. Food and Drug Administration (FDA) to be used only in certain U.S. patients with relapsed and refractory multiple myeloma that have tried and failed other therapies. Carfilzomib is considered an investigational drug for this study because the dose and regimen included in this study are different from the FDA approved carfilzomib regimen. Carfilzomib is a type of drug called a proteasome inhibitor. Carfilzomib is thought to work by preventing breakdown of abnormal proteins in cells, causing the cells to die. Cancer cells are more sensitive to these effects than normal cells. Carfilzomib has been previously given to more than 1800 people in clinical trials.
Read the detailed description
This is a Phase 2, multicenter, open label, non-randomized study to evaluate the safety and efficacy of a 30-minute infusion of 70 mg/m2 of carfilzomib among MM patients who are currently showing progressive disease (PD) and had failed their last treatment with twice weekly 27mg/m2 of carfilzomib alone or as part of a combination regimen.
The study will consist of 1) a screening period; 2) up to eight 28-day, treatment cycles; 3) maintenance treatment; 4) a final assessment to occur 28 days after the end of the last treatment cycle; and 5) a follow-up period. The study will enroll a total of 45 patients who are currently showing PD and had progressed within 8 weeks of receiving their last treatment with twice weekly 27mg/m2 of carfilzomib alone or as part of a combination regimen. Additionally, patients who have not achieved a complete response (CR) and have plateaued (as defined by unchanged disease markers for at least 8 weeks) while treated with a combination of carfilzomib (twice weekly 27 mg/m2), lenalidomide and dexamethasone; carfilzomib (twice weekly 27 mg/m2), pomalidomide and dexamethasone; or carfilzomib (twice weekly 27 mg/m2) and dexamethasone are also eligible for this study. Patients who were treated with a carfilzomib (twice weekly 27 mg/m2) containing combination who are currently on carfilzomib (twice weekly 27 mg/m2) and dexamethasone with or without lenalidomide or pomalidomide maintenance therapy and are not in CR and show unchanged disease markers for at least 8 weeks will also be eligible.
Patients will be enrolled from 15 hematology/oncology sites across the United States.
During the treatment period, all doses of carfilzomib will be given at 70 mg/m2 infused over 30 minutes. Among patients who received steroids at the equivalent of > 8 mg of dexamethasone weekly with carfilzomib, steroids will be administered using the same drug(s) at the same dose(s) and schedule(s) as they received during their previous carfilzomib treatment. Patients who did not receive steroids or received the equivalent of less than 8 mg of dexamethasone weekly will be given 8 mg of dexamethasone prior to each carfilzomib administration. Carfilzomib will be administered at a facility capable of managing hypersensitivity reactions. Pre- and post-dose intravenous (IV) hydration (between 250 mL and 500 mL normal saline or other appropriate IV fluid formulation) may be given at the discretion of the treating physician. Subjects should be monitored periodically during this period for evidence of fluid overload. Subjects who complete 8 cycles without showing PD will be eligible to receive maintenance therapy on a 28-day cycle with carfilzomib and steroids as administered during the last cycle of the treatment period. In addition, those treated with lenalidomide with carfilzomib and dexamethasone will continue lenalidomide at the same dose and schedule as used during the treatment period. For those treated with pomalidomide with carfilzomib and dexamethasone, pomalidomide will be administered at the same dose and schedule as during treatment.
During maintenance (cycle 9 and beyond), carfilzomib will be administered at the dose received during the last cycle of study treatment on Days 1, 8 and 15, and steroids will be administered using the same drug(s) at the same dose(s) and schedule(s) as given during the last cycle of study treatment. Patients will remain on maintenance therapy until documentation of PD as defined by the modified Bladé criteria or until they develop toxicity. Patients with stable disease (SD) will remain on maintenance therapy. Dose reductions of carfilzomib and steroids will be permitted as per protocol guidelines.
- Conditions
- Multiple Myeloma
- Being tested
- Carfilzomib, Dexamethasone, Prednisone, Methylprednisolone, Lenalidomide
- Keywords
- carfilzomib, proteasome inhibitor, multiple myeloma, relapsed/refractory
- 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.
CarfilzomibDrug
Also called Kyprolis
DexamethasoneDrug
Also called Decadron, Dexamethasone acetate
If the patient was receiving steroids at the equivalent of > 8 mg of dexamethasone weekly either intravenously (IV) or Per Orem (PO) in combination with carfilzomib, the same drug(s), dose(s) and schedule(s) of steroids will be continued. If the patient was not receiving steroids or was receiving less than the equivalent of 8 mg of dexamethasone weekly, then he/she will be given 8 mg of dexamethasone (IV or PO) prior to each carfilzomib administration.
PrednisoneDrug
Also called Deltasone, Cortan
f the patient was receiving prednisone, at the equivalent of > 8 mg of dexamethasone weekly PO in combination with carfilzomib, he/she will continue to receive prednisone at the same dose and schedule.
Also called Medrol, Methylprednisolone acetate
If the patient was receiving methylprednisolone at the equivalent of > 8 mg of dexamethasone weekly either IV or PO in combination with carfilzomib, he/she will continue to receive methylprednisolone at the same dose and schedule.
LenalidomideDrug
Also called Revlimid
given at same dose and schedule as patient was receiving while being treated with twice weekly carfilzomib at 27 mg/m2
PomalidomideDrug
Also called Pomalyst
administered PO at 4mg daily on days 1-21 of a 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Carfilzomib + Dexamethasone | Experimental | Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dexamethasone (IV or PO) will be given prior to each carfilzomib administration. Receives: Drug: Carfilzomib; Drug: Dexamethasone |
| Carfilzomib + Prednisone | Experimental | Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Prednisone (IV or PO) will be given prior to each carfilzomib administration. Receives: Drug: Carfilzomib; Drug: Prednisone |
| Carfilzomib + Methylprednisolone | Experimental | Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Methylprednisolone(IV or PO) will be given prior to each carfilzomib administration. Receives: Drug: Carfilzomib; Drug: Methylprednisolone |
| Carfilzomib+Lenalidomide+Dexamethasone | Experimental | Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dexamethasone (IV or PO) will be given prior to each carfilzomib administration. Lenalidomide will be given at the same dose and schedule as patient was receiving previously. Receives: Drug: Carfilzomib; Drug: Dexamethasone; Drug: Lenalidomide |
| Carfilzomib+Pomalidomide+Dexamethasone | Experimental | Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dexamethasone (IV or PO) will be given prior to each carfilzomib administration. Pomalidomide will be given PO at 4mg daily on days 1-21 of a 28-day cycle Receives: Drug: Carfilzomib; Drug: Dexamethasone; Drug: Pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
Complete response (CR)+ very good partial response (VGPR) + partial response (PR), defined using International Myeloma Working Group (IMWG) criteria
Measured: up to 30 months
Clinical Benefit Rate (CBR)
CBR=ORR + minor response (MR)
Measured: up to 30 months
Number of patients undergoing adverse events
Adverse events (AEs) graded via the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria
Measured: up to 36 months
Secondary outcomes (5)
Time to Progression (TTP)
Time from initiation of therapy to progressive disease
Measured: 36 months
Progression-Free Survival (PFS)
Time from initiation of therapy to progressive disease or death from any cause, whichever occurs first
Measured: 36 months
Time to Response (TTR)
Time from the initiation of therapy to the first evidence of a confirmed response
Measured: 36 months
Duration of Response (DOR)
Time from the first response (> PR) to progressive disease
Measured: 36 months
Overall Survival (OS)
Time from initiation of therapy to death from any cause or last follow-up visit
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2014 (estimated)
- Study startDec 2014
- Primary completion21 Sep 2020
- Study completion22 Sep 2020
Why it stopped: Early termination due to the difficulties to enroll subjects.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oncotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- James R Berenson, MD, Principal investigator, James R. Berenson MD, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02294357
- Sponsor's protocol ID
- IST-CAR-2014-100701 (20159897)
- Status last verified
- Oct 2023
- First submitted
- 10 Nov 2014
- Last updated
- 1 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: Demographics and Clinical Responses
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Weekly 70 mg/m2 Carfilzomib for Multiple Myeloma Patients Refractory to 27 mg/m2 Carfilzomib
- ClinicalTrials.gov ID
- NCT02294357
- Acronym / sponsor ID
- IST-CAR-2014-100701 (20159897)
- Conditions
- Multiple Myeloma
- Keywords
- carfilzomib, proteasome inhibitor, multiple myeloma, relapsed/refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early termination due to the difficulties to enroll subjects.
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- OncotherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Amgen
- Study start
- Dec 2014
- Primary completion
- 21 Sep 2020 (actual)
- Study completion
- 22 Sep 2020 (actual)
- First posted
- 19 Nov 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 purpose of this Phase II study is to evaluate the safety and effectiveness (good and bad effects) of carfilzomib given as a 30-minute infusion and at a dose of 70 mg/m2 to treat patients with multiple myeloma (MM), who are currently showing progressive disease (worsening) and had progressed (did not respond to treatment) within 8 weeks of receiving treatment with twice weekly 27mg/m2 of carfilzomib. Carfilzomib is approved by the U.S. Food and Drug Administration (FDA) to be used only in certain U.S. patients with relapsed and refractory multiple myeloma that have tried and failed other therapies. Carfilzomib is considered an investigational drug for this study because the dose and regimen included in this study are different from the FDA approved carfilzomib regimen. Carfilzomib is a type of drug called a proteasome inhibitor. Carfilzomib is thought to work by preventing breakdown of abnormal proteins in cells, causing the cells to die. Cancer cells are more sensitive to these effects than normal cells. Carfilzomib has been previously given to more than 1800 people in clinical trials.
Detailed description
This is a Phase 2, multicenter, open label, non-randomized study to evaluate the safety and efficacy of a 30-minute infusion of 70 mg/m2 of carfilzomib among MM patients who are currently showing progressive disease (PD) and had failed their last treatment with twice weekly 27mg/m2 of carfilzomib alone or as part of a combination regimen.
The study will consist of 1) a screening period; 2) up to eight 28-day, treatment cycles; 3) maintenance treatment; 4) a final assessment to occur 28 days after the end of the last treatment cycle; and 5) a follow-up period. The study will enroll a total of 45 patients who are currently showing PD and had progressed within 8 weeks of receiving their last treatment with twice weekly 27mg/m2 of carfilzomib alone or as part of a combination regimen. Additionally, patients who have not achieved a complete response (CR) and have plateaued (as defined by unchanged disease markers for at least 8 weeks) while treated with a combination of carfilzomib (twice weekly 27 mg/m2), lenalidomide and dexamethasone; carfilzomib (twice weekly 27 mg/m2), pomalidomide and dexamethasone; or carfilzomib (twice weekly 27 mg/m2) and dexamethasone are also eligible for this study. Patients who were treated with a carfilzomib (twice weekly 27 mg/m2) containing combination who are currently on carfilzomib (twice weekly 27 mg/m2) and dexamethasone with or without lenalidomide or pomalidomide maintenance therapy and are not in CR and show unchanged disease markers for at least 8 weeks will also be eligible.
Patients will be enrolled from 15 hematology/oncology sites across the United States.
During the treatment period, all doses of carfilzomib will be given at 70 mg/m2 infused over 30 minutes. Among patients who received steroids at the equivalent of > 8 mg of dexamethasone weekly with carfilzomib, steroids will be administered using the same drug(s) at the same dose(s) and schedule(s) as they received during their previous carfilzomib treatment. Patients who did not receive steroids or received the equivalent of less than 8 mg of dexamethasone weekly will be given 8 mg of dexamethasone prior to each carfilzomib administration. Carfilzomib will be administered at a facility capable of managing hypersensitivity reactions. Pre- and post-dose intravenous (IV) hydration (between 250 mL and 500 mL normal saline or other appropriate IV fluid formulation) may be given at the discretion of the treating physician. Subjects should be monitored periodically during this period for evidence of fluid overload. Subjects who complete 8 cycles without showing PD will be eligible to receive maintenance therapy on a 28-day cycle with carfilzomib and steroids as administered during the last cycle of the treatment period. In addition, those treated with lenalidomide with carfilzomib and dexamethasone will continue lenalidomide at the same dose and schedule as used during the treatment period. For those treated with pomalidomide with carfilzomib and dexamethasone, pomalidomide will be administered at the same dose and schedule as during treatment.
During maintenance (cycle 9 and beyond), carfilzomib will be administered at the dose received during the last cycle of study treatment on Days 1, 8 and 15, and steroids will be administered using the same drug(s) at the same dose(s) and schedule(s) as given during the last cycle of study treatment. Patients will remain on maintenance therapy until documentation of PD as defined by the modified Bladé criteria or until they develop toxicity. Patients with stable disease (SD) will remain on maintenance therapy. Dose reductions of carfilzomib and steroids will be permitted as per protocol guidelines.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Carfilzomib + Dexamethasone | Experimental | Drug: Carfilzomib, Drug: DexamethasoneCarfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dexamethasone (IV or PO) will be given prior to each carfilzomib administration. |
| Carfilzomib + Prednisone | Experimental | Drug: Carfilzomib, Drug: PrednisoneCarfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Prednisone (IV or PO) will be given prior to each carfilzomib administration. |
| Carfilzomib + Methylprednisolone | Experimental | Drug: Carfilzomib, Drug: MethylprednisoloneCarfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Methylprednisolone(IV or PO) will be given prior to each carfilzomib administration. |
| Carfilzomib+Lenalidomide+Dexamethasone | Experimental | Drug: Carfilzomib, Drug: Dexamethasone, Drug: LenalidomideCarfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dexamethasone (IV or PO) will be given prior to each carfilzomib administration. Lenalidomide will be given at the same dose and schedule as patient was receiving previously. |
| Carfilzomib+Pomalidomide+Dexamethasone | Experimental | Drug: Carfilzomib, Drug: Dexamethasone, Drug: PomalidomideCarfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dexamethasone (IV or PO) will be given prior to each carfilzomib administration. Pomalidomide will be given PO at 4mg daily on days 1-21 of a 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (38 listed)
- Has a diagnosis of MM based on standard criteria as follows:
- Patient must meet one of the following:
- Patient must have received at least one full cycle of carfilzomib at a dose of twice weekly 27mg/m2 prior to showing evidence of PD or plateauing from their last carfilzomib-containing regimen.
- Patient must have previously received treatment with an immunomodulatory agents lenalidomide or pomalidomide to be eligible for the study (applicable only for subjects who qualify via inclusion criteria 2B or 2C).
- There is no limit to the number of prior lines of therapy that a patient may have received.
Key exclusion criteria (34 listed)
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential)
- Waldenström's macroglobulinemia
- Amyloidosis
- Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to first dose
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 |
|---|---|---|
| CarfilzomibAlso: Kyprolis | Drug | Carfilzomib + Dexamethasone, Carfilzomib + Methylprednisolone, Carfilzomib + Prednisone, Carfilzomib+Lenalidomide+Dexamethasone, Carfilzomib+Pomalidomide+Dexamethasone |
| DexamethasoneAlso: Decadron, Dexamethasone acetateIf the patient was receiving steroids at the equivalent of > 8 mg of dexamethasone weekly either intravenously (IV) or Per Orem (PO) in combination with carfilzomib, the same drug(s), dose(s) and schedule(s) of steroids will be continued. If the patient was not receiving steroids or was receiving less than the equivalent of 8 mg of dexamethasone weekly, then he/she will be given 8 mg of dexamethasone (IV or PO) prior to each carfilzomib administration. | Drug | Carfilzomib + Dexamethasone, Carfilzomib+Lenalidomide+Dexamethasone, Carfilzomib+Pomalidomide+Dexamethasone |
| PrednisoneAlso: Deltasone, Cortanf the patient was receiving prednisone, at the equivalent of > 8 mg of dexamethasone weekly PO in combination with carfilzomib, he/she will continue to receive prednisone at the same dose and schedule. | Drug | Carfilzomib + Prednisone |
| MethylprednisoloneAlso: Medrol, Methylprednisolone acetateIf the patient was receiving methylprednisolone at the equivalent of > 8 mg of dexamethasone weekly either IV or PO in combination with carfilzomib, he/she will continue to receive methylprednisolone at the same dose and schedule. | Drug | Carfilzomib + Methylprednisolone |
| LenalidomideAlso: Revlimidgiven at same dose and schedule as patient was receiving while being treated with twice weekly carfilzomib at 27 mg/m2 | Drug | Carfilzomib+Lenalidomide+Dexamethasone |
| PomalidomideAlso: Pomalystadministered PO at 4mg daily on days 1-21 of a 28 day cycle | Drug | Carfilzomib+Pomalidomide+Dexamethasone |
Primary outcome
Overall response rate (ORR)
Time frame: up to 30 months
Complete response (CR)+ very good partial response (VGPR) + partial response (PR), defined using International Myeloma Working Group (IMWG) criteria
Clinical Benefit Rate (CBR)
Time frame: up to 30 months
CBR=ORR + minor response (MR)
Number of patients undergoing adverse events
Time frame: up to 36 months
Adverse events (AEs) graded via the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria
5 secondary outcomes
Time to Progression (TTP)
Time frame: 36 months
Progression-Free Survival (PFS)
Time frame: 36 months
Time to Response (TTR)
Time frame: 36 months
Duration of Response (DOR)
Time frame: 36 months
Overall Survival (OS)
Time frame: 36 months
Results and safety
The study was stopped early (reason given: Early termination due to the difficulties to enroll subjects.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2023.
- Individual participant dataSharing planned: No. Demographics and Clinical Responses
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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.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carfilzomib, Dexamethasone and Prednisone in people with Multiple Myeloma, run by Oncotherapeutics at 7 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 38 inclusion and 34 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: stopped early, as of the sponsor's last update on 1 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 phase mean?
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 was stopped early (reason given: Early termination due to the difficulties to enroll subjects.). Results are not available in the source record.
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?
Overall response rate (ORR) (time frame: up to 30 months). The study lists 3 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 1 Nov 2023.