A Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma (CHAMPION 1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier:
NCT01677858
First received: August 30, 2012
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

This is a Phase 1/2, multicenter, single-arm, nonrandomized, open-label and dose-escalation study of weekly carfilzomib and dexamethasone (Cd-qw) for patients with progressive multiple myeloma. The Phase 1 dose escalation portion will enroll patients into sequential dose-escalating cohorts consisting of 3 patients each to establish the maximum tolerated dose (MTD) of carfilzomib administered weekly as a 30 minute intravenous (IV) infusion with dexamethasone. The Phase 2 portion will enroll patients using the MTD established for carfilzomib from the Phase 1 portion of the study. Dexamethasone will be administered IV or PO at the same dose and schedule as used in the Phase 1 portion of the study.


Condition Intervention Phase
Multiple Myeloma
Drug: carfilzomib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2, Multicenter, Single-arm, Nonrandomized, Open-label and Dose-escalation Study of Weekly Carfilzomib and Dexamethasone (Cd-qw) for Patients With Progressive Multiple Myeloma.

Resource links provided by NLM:


Further study details as provided by Onyx Pharmaceuticals:

Primary Outcome Measures:
  • Phase 1: Determine the Maximum Tolerated Dose [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Phase 1: Determine the MTD for patients with progressive multiple myeloma treated with weekly carfilzomib and dexamethasone.

  • Phase 2: Overall Response Rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Phase 2: Estimate the overall response rate (ORR, defined as the proportion of patients who achieve a confirmed PR or better) for patients with progressive multiple myeloma treated with weekly carfilzomib and dexamethasone.


Secondary Outcome Measures:
  • Clinical Benefit Response Rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Estimate the clinical benefit response rate (CBR) in accordance with IMWG Criteria

  • Progression Free Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Estimate the progression-free survival (PFS)

  • Time To Progression [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Estimate the time to progression (TTP)

  • Duration of Response [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Estimate the duration of response (DOR)


Estimated Enrollment: 123
Study Start Date: July 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: carfilzomib

Phase 1: Carfilzomib will be administered as a 30-minute intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle. On only Day 1 of Cycle 1, all patients will receive carfilzomib at 20 mg/m2. All subsequent carfilzomib doses (45, 56, 70 or 88 mg/m2) will be administered according to the dose assignment for each cohort.

Phase 2: using the MTD established for carfilzomib from the Phase 1 portion of the study (except on Cycle 1 Day 1 the carfilzomib dose will be 20 mg/m2); this arm will be administered drug on the same schedule as in Phase 1.

Drug: carfilzomib

Detailed Description:

This Phase 1/2 study in patients with progressive multiple myeloma is designed to achieve the following: to determine the MTD of carfilzomib and dexamethasone administered once weekly (Cd-qw) for 3 consecutive weeks in a 28-day cycle and to determine the magnitude of responses achieved in patients treated with the MTD.

The Cd-qw dosing schedule proposed in this protocol may be beneficial from a patient convenience perspective compared to the twice-weekly dosing schedule, however, as the clinical benefit and safety of weekly carfilzomib administration has not been assessed in multiple myeloma patients, patients who progress on weekly carfilzomib will be allowed 1 attempt to recapture response by increasing the dose frequency to the twice-weekly carfilzomib dosing schedule that has demonstrated efficacy and tolerability. This information will be valuable in assessing the dose intensity impact on the suppression of multiple myeloma in the relapsed setting.

Finally, this protocol will eliminate the requirement for fluid administration with carfilzomib after Cycle 1 and will reduce the time that is required to treat the patient in clinic. This modification will be studied for its effect on the carfilzomib safety profile.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Multiple myeloma with relapsing or progressive disease at study entry
  2. Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to enrollment):

    1. Serum M-protein ≥ 0.5 g/dL, or
    2. Urine M-protein ≥ 200 mg/24 hours, or
    3. 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 kappa/lambda ratio
  3. Prior treatment with 1 to 3 prior regimens for multiple myeloma for Phase 1 and Phase 2 (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy
  4. Age ≥ 18 years
  5. Life expectancy ≥ 6 months
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  7. Adequate hepatic function within 21 days prior to enrollment, with bilirubin < 1.5 × the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 × ULN
  8. Left ventricular ejection fraction (LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated acquisition scan (MUGA) is acceptable if ECHO is not available
  9. Absolute neutrophil count (ANC) ≥ 1000/mm3 within 21 days prior to enrollment. Screening ANC is to be independent of growth factor support for ≥ 1 week
  10. Hemoglobin ≥ 8.0 g/dL within 21 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
  11. Platelet count ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is > 50%) within 21 days prior to enrollment. Patients must not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count
  12. Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min within 21 days prior to enrollment. Calculation are to be based on standard formula, such as the Cockcroft and Gault: [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female
  13. Written informed consent in accordance with federal, local, and institutional guidelines
  14. Female patients of childbearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use an effective method of contraception during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations). Postmenopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test
  15. Male patients must agree to use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with an FCBP

Exclusion Criteria:

  1. 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 enrollment
  7. Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to enrollment
  8. Treatment with bortezomib (Velcade®), thalidomide (Thalomid®) or lenalidomide (Revlimid®) within 21 days prior to enrollment
  9. Focal radiation therapy within 7 days prior to enrollment. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (ie, prior radiation must have been to < 30% of the bone marrow)
  10. Immunotherapy within 21 days prior to enrollment
  11. Major surgery within 21 days prior to enrollment
  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 enrollment
  13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at HBV), or antifungal agents within 14 days prior to enrollment
  14. Known human immunodeficiency virus (HIV) seropositivity
  15. Known hepatitis B or C virus infection (except for patients with HBV who are 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:

    1. Adequately treated basal cell or squamous cell skin cancer
    2. Carcinoma in situ of the cervix
    3. Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
    4. Breast carcinoma in situ with full surgical resection
    5. Treated medullary or papillary thyroid cancer
  18. Patients with myelodysplastic syndrome
  19. Significant neuropathy (Grades 3 to 4) within 14 days prior to enrollment
  20. Female patients who are pregnant or lactating
  21. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
  22. Prior carfilzomib treatment
  23. Prior participation in any Onyx-sponsored Phase 3 trial
  24. Patients with contraindication to dexamethasone
  25. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
  26. Ongoing graft-versus-host disease
  27. Patients with 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: NCT01677858

  Show 43 Study Locations
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Investigators
Study Director: Priti Patel, MD Onyx Therapeutics Medical Monitor
  More Information

No publications provided

Responsible Party: Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier: NCT01677858     History of Changes
Other Study ID Numbers: 2012-002
Study First Received: August 30, 2012
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration

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
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 18, 2014