This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback
Trial record 1 of 32 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

This study is currently recruiting participants.
See Contacts and Locations
Verified November 2016 by Oncotherapeutics
Sponsor:
Collaborator:
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
Oncotherapeutics
ClinicalTrials.gov Identifier:
NCT02294357
First received: November 10, 2014
Last updated: November 17, 2016
Last verified: November 2016
  Purpose
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 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 Intervention Phase
Multiple Myeloma Drug: Carfilzomib Drug: Dexamethasone Drug: Prednisone Drug: Methylprednisolone Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Oncotherapeutics:

Primary Outcome Measures:
  • 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


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

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

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

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

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


Estimated Enrollment: 45
Study Start Date: December 2014
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carfilzomib and 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 and 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 and 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

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 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 27mg/m2 of carfilzomib alone or as part of a combination regimen. 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 that 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.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.

  Eligibility

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 criteria1 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. Currently has progressive MM that has progressed while receiving or within 8 weeks of receiving carfilzomib 27mg/m2 alone or as part of their last carfilzomib-containing combination regimens.
  3. Patient must have received at least one full cycle of carfilzomib at a dose of 27mg/m2 prior to showing evidence of PD from their last carfilzomib-containing regimen.
  4. Patient must have previously received treatment with an immunomodulatory agent to be eligible for the study.
  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:

Multiple myeloma of IgM subtype 2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 3. Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential) 4. Waldenström's macroglobulinemia 5. Amyloidosis 6. Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to first dose 7. Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to first dose 8. Treatment with bortezomib (Velcade®), thalidomide, pomalidomide (Pomalyst®) or lenalidomide (Revlimid®) within 21 days prior to first dose 9. 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) 10. Immunotherapy within 21 days prior to first dose 11. Major surgery within 21 days prior to first dose 12. 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 13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at HBV), or antifungal agents within 14 days prior to first dose 14. Known human immunodeficiency virus (HIV) seropositivity 15. Known active hepatitis B or C virus infection (except for patients with HBV receiving and responding to HBV antiviral therapy: these patients are allowed) 16. Patients with known cirrhosis 17. 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 18. Patients with myelodysplastic syndrome 19. Significant neuropathy (Grades 3 to 4) within 14 days prior to first dose 20. Peripheral neuropathy with pain ≥ G2 within 14 days prior to first dose 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.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02294357

Contacts
Contact: Diana Pelipad, MD 310-623-1209 ext 130 dpelipad@oncotherapeutics.com
Contact: Tanya M Spektor, PhD 424-204-0737 ext 252 tspektor@oncotherapeutics.com

Locations
United States, California
James R Berenson, MD, Inc. Recruiting
West Hollywood, California, United States, 90069
Contact: James Berenson, MD    310-623-1222    jberenson@imbcr.org   
Contact: Regina Swift, RN, BSN    310-623-1222    rswift@berensononcology.com   
Sub-Investigator: Youram Nassir, MD         
Sub-Investigator: Shahrooz Eshaghian, MD         
Principal Investigator: James Berenson, MD         
Sponsors and Collaborators
Oncotherapeutics
Onyx Therapeutics, Inc.
Investigators
Principal Investigator: James R Berenson, MD James R. Berenson MD, Inc.
  More Information

Responsible Party: Oncotherapeutics
ClinicalTrials.gov Identifier: NCT02294357     History of Changes
Other Study ID Numbers: IST-CAR-2014-100701
Study First Received: November 10, 2014
Last Updated: November 17, 2016

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
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 19, 2017