ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 35 for:    27 mg/m2 Carfilzomib
Previous Study | Return to List | Next Study

Weekly 70 mg/m2 Carfilzomib for Multiple Myeloma Patients Refractory to 27 mg/m2 Carfilzomib

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02294357
Recruitment Status : Recruiting
First Posted : November 19, 2014
Last Update Posted : March 15, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Oncotherapeutics

Brief 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 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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Carfilzomib Drug: Dexamethasone Drug: Prednisone Drug: Methylprednisolone Drug: Lenalidomide Drug: Pomalidomide Phase 2

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Weekly 70 mg/m2 Carfilzomib for Multiple Myeloma Patients Refractory to 27 mg/m2 Carfilzomib
Study Start Date : December 2014
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Carfilzomib
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Carfilzomib + Dexamethasone
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.
Drug: Carfilzomib
Other Name: Kyprolis
Drug: Dexamethasone
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.
Other Names:
  • Decadron
  • Dexamethasone acetate
Experimental: Carfilzomib + Prednisone
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.
Drug: Carfilzomib
Other Name: Kyprolis
Drug: Prednisone
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.
Other Names:
  • Deltasone
  • Cortan
Experimental: Carfilzomib + Methylprednisolone
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.
Drug: Carfilzomib
Other Name: Kyprolis
Drug: Methylprednisolone
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.
Other Names:
  • Medrol
  • Methylprednisolone acetate
Experimental: Carfilzomib+Lenalidomide+Dexamethasone
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.
Drug: Carfilzomib
Other Name: Kyprolis
Drug: Dexamethasone
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.
Other Names:
  • Decadron
  • Dexamethasone acetate
Drug: Lenalidomide
given at same dose and schedule as patient was receiving while being treated with twice weekly carfilzomib at 27 mg/m2
Other Name: Revlimid
Experimental: Carfilzomib+Pomalidomide+Dexamethasone
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
Drug: Carfilzomib
Other Name: Kyprolis
Drug: Dexamethasone
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.
Other Names:
  • Decadron
  • Dexamethasone acetate
Drug: Pomalidomide
administered PO at 4mg daily on days 1-21 of a 28 day cycle
Other Name: Pomalyst



Primary Outcome Measures :
  1. 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

  2. Clinical Benefit Rate (CBR) [ Time Frame: up to 30 months ]
    CBR=ORR + minor response (MR)

  3. 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


Secondary Outcome Measures :
  1. Time to Progression (TTP) [ Time Frame: 36 months ]
    Time from initiation of therapy to progressive disease

  2. Progression-Free Survival (PFS) [ Time Frame: 36 months ]
    Time from initiation of therapy to progressive disease or death from any cause, whichever occurs first

  3. Time to Response (TTR) [ Time Frame: 36 months ]
    Time from the initiation of therapy to the first evidence of a confirmed response

  4. Duration of Response (DOR) [ Time Frame: 36 months ]
    Time from the first response (> PR) to progressive disease

  5. Overall Survival (OS) [ Time Frame: 36 months ]
    Time from initiation of therapy to death from any cause or last follow-up visit



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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:

    • 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
  2. 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
  3. 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.
  4. 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).
  5. There is no limit to the number of prior lines of therapy that a patient may have received.
  6. 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
  7. Age ≥ 18 years.
  8. Life expectancy ≥ 6 months.
  9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  10. 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.
  11. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. Written informed consent in accordance with federal, local, and institutional guidelines.
  17. 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
  18. 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.

Exclusion Criteria:

  1. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  2. Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential)
  3. Waldenström's macroglobulinemia
  4. Amyloidosis
  5. Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to first dose
  6. Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to first dose
  7. Treatment with bortezomib (Velcade®), thalidomide, pomalidomide (Pomalyst®) or lenalidomide (Revlimid®) within 21 days prior to first dose
  8. 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)
  9. Immunotherapy within 21 days prior to first dose
  10. Major surgery within 21 days prior to first dose
  11. 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
  12. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at HBV), or antifungal agents within 14 days prior to first dose
  13. Known human immunodeficiency virus (HIV) seropositivity
  14. Known active hepatitis B or C virus infection (except for patients with HBV receiving and responding to HBV antiviral therapy: these patients are allowed)
  15. Patients with known cirrhosis
  16. 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
  17. Patients with myelodysplastic syndrome
  18. Significant neuropathy (Grades 3 to 4) within 14 days prior to first dose
  19. Peripheral neuropathy with pain ≥ G2 within 14 days prior to first dose
  20. Patients with baseline hepatic impairment
  21. Women who are pregnant and/or breast feeding
  22. Known hypersensitivity to dexamethasone
  23. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
  24. Hypersensitivity to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs.
  25. Prior participation in any Onyx-sponsored Phase 3 trial
  26. Ongoing graft-versus-host disease
  27. Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment
  28. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
  29. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02294357


Contacts
Contact: Noemi Silagan 310-623-1200 nsilagan@oncotherapeutics.com
Contact: Alexa Cohen 310-623-1200 acohen@oncotherapeutics.com

Locations
United States, California
California Cancer Associates for Research & Excellence (cCARE) Recruiting
Encinitas, California, United States, 92024
Contact: Alberto Bessudo, MD         
Contact: Beth Kimball, RN    (760) 452-3909    BKimball@ccare.com   
Wellness Oncology and Hematology Recruiting
West Hills, California, United States, 91307
Contact: Ashkan Lashkari, MD         
Contact: Mary Mau    (818) 346-1773    mary@wellnessoncology.com   
James R Berenson, MD, Inc. Recruiting
West Hollywood, California, United States, 90069
Contact: James Berenson, MD         
Contact: Regina Swift, RN, BSN    310-623-1222    rswift@berensononcology.com   
United States, Florida
Cancer Specialists of North Florida Recruiting
Fleming Island, Florida, United States, 32003
Contact: Mehdi Moezi, MD         
Contact: Jenni Bachhofer    (904) 363-7462    Jenni.Bachhofer@CSNF.us   
United States, New York
Hudson Valley Hem/Onc Associates Completed
Poughkeepsie, New York, United States, 12601
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Nashat Gabrail, MD         
Contact: Kirstie Armstrong    (330) 492-3345    karmstrong@gabrailcancercenter.com   
United States, Texas
Blood & Cancer Center of East Texas Completed
Tyler, Texas, United States, 75701
Sponsors and Collaborators
Oncotherapeutics
Amgen
Investigators
Principal Investigator: James R Berenson, MD James R. Berenson MD, Inc.

Responsible Party: Oncotherapeutics
ClinicalTrials.gov Identifier: NCT02294357     History of Changes
Other Study ID Numbers: IST-CAR-2014-100701 (20159897)
First Posted: November 19, 2014    Key Record Dates
Last Update Posted: March 15, 2018
Last Verified: March 2018

Keywords provided by Oncotherapeutics:
carfilzomib
proteasome inhibitor
multiple myeloma
relapsed/refractory

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Prednisolone acetate
Methylprednisolone acetate
Dexamethasone
Prednisone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Lenalidomide
Pomalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics