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A Study of Carfilzomib Plus Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma at US Community Oncology Centers

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ClinicalTrials.gov Identifier: NCT03512353
Recruitment Status : Active, not recruiting
First Posted : April 30, 2018
Last Update Posted : August 8, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
Describe the safety profile of carfilzomib plus dexamethasone regimen (Kd 56 mg/m2 twice weekly in cycles 1-6 followed by Kd 70 mg/m2 once weekly in cycles 7-12) in subjects with RRMM with 1-3 prior lines of therapy at study entry.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Multiple Myeloma Combination Product: Dexamethasone Combination Product: Carfilzomib Phase 2

Detailed Description:
This is a phase 2, multicenter, open-label study in subjects with RRMM in US community oncology centers. Subjects with 1-3 prior lines of therapy at study entry are eligible to be screened for participation. Subjects refractory to their last line of treatment are eligible to participate as long as their last line of treatment did not include a proteasome inhibitor (PI). The study will consist of a screening period of up to 28 days for bone marrow assessments and up to 21 days for all other assessments, up to 12 cycles of treatment, and a 30-day safety follow-up period following the last dose of study drug. During the treatment period, all subjects will be treated with Kd 20/56 mg/m2 twice weekly for up to six 28-day cycles followed by up to Kd 70 mg/m2 once weekly for another six 28-day cycles. After discontinuation of study drugs, subjects will be followed for 30 days for safety.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase 2 Study of Carfilzomib Plus Dexamethasone To Assess Tolerability and Adherence in Subjects With Relapsed or Refractory Multiple Myeloma at US Community Oncology Centers
Actual Study Start Date : July 5, 2018
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : February 28, 2020


Arm Intervention/treatment
Experimental: Carfilzomib Plus Dexamethasone
Describe the safety profile of carfilzomib plus dexamethasone regimen (Kd 56 mg/m2 twice weekly for cycles 1-6 followed by Kd 70 mg/m2 once weekly for cycles 7-12) in subjects with relapsed or refractory multiple myeloma (RRMM) with 1-3 prior lines of therapy at study entry. Describe subjects' adherence by evaluating a carfilzomib plus dexamethasone twice-weekly dosing regimen followed by a once-weekly dosing regimen.
Combination Product: Dexamethasone
Describe subject´s adherence by evaluating a carfilzomib plus dexamethasone twice-weekly dosing regimen followed by a once-weekly dosing regimen.

Combination Product: Carfilzomib
Describe subject´s adherence by evaluating a carfilzomib plus dexamethasone twice-weekly dosing regimen followed by a once-weekly dosing regimen.




Primary Outcome Measures :
  1. Proportion of subjects completing [ Time Frame: 12 cycles (each cycle is 28 days) ]
    Proportion of subjects completing 12 cycles of treatment

  2. Cumulative Dose [ Time Frame: Up to 12 cycles (each cycles is 28 days) ]
    proportion of actual cumulative dose received to the full intended cumulative dose in cycles 1-12

  3. Relative Dose Intensity [ Time Frame: Up to 12 Cycles (each cycle is 28 days) ]
    relative dose intensity in cycles 1-12

  4. Treatment - Emergent [ Time Frame: Up to 12 Cycles (each cycle is 28 days) ]
    dose modifications and reasons in cycles 1-12 treatment-emergent adverse events and serious adverse events


Secondary Outcome Measures :
  1. Dose intensity [ Time Frame: Within each treatment cycle 1-6 and 7-12 (each cycle is 28 days) ]
    Proportion of actual cumulative dose received to the full intended cumulative dose in cycles 1-6 and 7-12

  2. Dose Intensity [ Time Frame: Within each treatment cycle 1-6 and 7-12 (each cycle is 28 days) ]
    Relative dose intensity in cycles 1-6 and cycles 7-12

  3. Dose reduction [ Time Frame: Within each treatment cycle 1-6 and 7-12 (each cycle is 28 days) ]
    Dose modifications in cycles 1-6 and cycles 7-12

  4. Treatment discontinuation [ Time Frame: Within each treatment cycle 1-6 and 7-12 (each cycle is 28 days) ]
    Treatment discontinuation for all reasons in cycles 1-6 and cycles 7-12

  5. Assess response to the Kd regimen [ Time Frame: Within each treatment cycle 1-6 and 7-12 (each cycle is 28 days) ]
    response rate (stringent complete response sCR, complete response CR, very good partial response VGPR, partial response PR, minimal response [MR], stable disease SD, progressive disease PD, Not evaluable NE. Landmark response rate (sCR, CR, VGPR, PR, MR, SD, PD, NE) at the end of Kd twice weekly and once weekly regimen.

  6. Assess response to the Kd regimen [ Time Frame: At one year ]
    Progression-free survival (PFS) at 1 year

  7. Assess response to the Kd regimen [ Time Frame: At one year ]
    Response rate by line of prior therapy 1 vs 2 or greater

  8. Assess response to the Kd regimen [ Time Frame: At one year ]
    PFS by line of prior therapy 1 vs 2 or greater



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Subject has provided informed consent prior to initiation of any study specific activities/procedures.
  • Males or females greater than or equal to 18 years of age.
  • Relapsed MM after last treatment or refractory while receiving non-proteasome inhibitor therapy.
  • Measurable disease with at least 1 of the following assessed within 21 days prior to enrollment: immunoglobulin G (IgG) MM: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL IgA, IgD, IgE multiple myeloma: serum M protein level ≥ 0.5 g/dL urine M-protein ≥ 200 mg per 24 hours in subjects without measurable serum or urine M-protein, serum free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.
  • Subjects must have at least partial response (PR) to at least 1 line of prior therapy.
  • Subjects must have received at least 1 but not more than 3 prior lines of therapy for MM (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy; see Section 12.11).
  • Prior therapy with a PI is allowed as long as the subject had at least a PR to most recent therapy with PI, was not removed due to toxicity (except for neuropathy, see criterion 213), did not relapse within 60 days from discontinuation of PI, and will have at least a 6-month PI treatment-free interval from last dose received until enrollment. (Subjects may receive maintenance therapy with drugs that are not PI during this 6-month PI treatment-free interval).

Exclusion Criteria:

  • Waldenström macroglobulinemia.
  • Multiple myeloma of IgM subtype.
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  • History of plasma cell leukemia.
  • Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met).
  • Subjects with nephrotic range proteinuria (greater than or equal to 3 g albumin for 24 hours urine OR greater than or equal to 2 g albumin/1 g of creatinine on a random urine specimen).
  • Myelodysplastic syndrome.
  • History of other malignancy within the past 5 years, with the following exceptions:

Malignancy treated with curative intent and with no known active disease present for greater than or equal to 3 years before enrollment and felt to be at low risk for recurrence by the treating physician. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated cervical carcinoma in situ without evidence of disease. Adequately treated breast ductal carcinoma in situ without evidence of disease. Prostatic intraepithelial neoplasia without evidence of prostate cancer. Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ. Treated medullary or papillary thyroid cancer. Similar neoplastic conditions with an expectation of greater than 95% five-year disease-free survival.

  • Known HIV infection, hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response following antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response with antiviral therapy directed at hepatitis B are allowed).
  • .Acute or chronic graft-versus-host disease (any grade).
  • Acute active infection requiring systemic antibiotics, antifungal, antiviral (except antiviral therapy directed at hepatitis B) agents within 14 days prior to enrollment.
  • Known cirrhosis.
  • Significant neuropathy (grades 3 to 4, or grade 2 with pain) within 14 days prior to enrollment.
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment.
  • Uncontrolled hypertension, defined as an average systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg (see Section 12.12 for more details). Subjects with controlled hypertension are eligible.
  • Hepatic dysfunction within 21 days prior to enrollment (see Section 7.1.1.2.1): bilirubin 1.5 times the upper limit of normal (ULN) aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 3 times the ULN
  • Active congestive heart failure with or without reduced ejection fraction (NYHA Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval (QTc) of greater than 470 msec, pericardial disease, myocardial infarction within 4 months prior to enrollment.
  • Known chronic obstructive pulmonary disease.
  • Known interstitial pneumonitis.
  • Immunotherapy within 21 days prior to enrollment.
  • Chemotherapy with approved anticancer therapeutic within 21 days prior to enrollment.
  • Glucocorticoid therapy (prednisone greater than 30 mg/day or equivalent) within 14 days prior to enrollment.
  • 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 less than 30% of the bone marrow).
  • Major surgery (except kyphoplasty) within 28 days prior to enrollment.
  • Autologous or allogeneic stem cell transplant within 90 days prior to enrollment.
  • Contraindication to dexamethasone.
  • Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib).
  • Intolerance to intravenous (IV) hydration.
  • Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
  • Hepatic dysfunction within 21 days prior to enrollment: bilirubin greater than or equal to 1.5 times the upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to 3 times the ULN.
  • Left ventricular ejection fraction less than 40% assessed by transthoracic echocardiogram.
  • Severe valvular disease assessed by transthoracic echocardiogram.
  • Severe right-ventricular dysfunction assessed by transthoracic echocardiogram.
  • Right-ventricular systolic pressure greater than 40 mm Hg assessed by transthoracic echocardiogram.
  • Screening ANC should be independent of growth factor support for greater than or equal to 1 week.
  • Hemoglobin less than 80 g/L 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 may not have been done within 7 days prior to obtaining screening hemoglobin.
  • Platelet count < 50 x 109/L ( ≤ 30 x 109/L if myeloma involvement in the bone marrow is > 50%) within 21 days prior to enrollment. Subjects should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count.
  • Estimated GFR less than 30 mL/min/1.73 m2 (per the Chronic Kidney Disease Epidemiology Collaboration formula, see Section 12.13) within 21 days prior to enrollment.

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): NCT03512353


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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03512353     History of Changes
Other Study ID Numbers: 20170596
First Posted: April 30, 2018    Key Record Dates
Last Update Posted: August 8, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors