Clinical trial NCT03512353: A Study of Carfilzomib Plus Dexamethasone in Adults With Relapsed or Refractory Multiple Myeloma at US Community Oncology Centers
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Relapsed or Refractory Multiple Myeloma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-04-30
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective was to describe the safety profile of carfilzomib plus dexamethasone regimen in adults with relapsed or refractory multiple myeloma (RRMM) with 1 to 3 prior lines of therapy at study entry.

Detailed description: This is a phase 2, multicenter, open-label study in adults with RRMM in US community oncology centers. Adults with 1-3 prior lines of therapy at study entry are eligible to be screened for participation. Patients 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.

Eligibility 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).
* Prior therapy with a proteasome inhibitor (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), 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 human immunodeficiency virus (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. Subjects with controlled hypertension are eligible.
* Hepatic dysfunction within 21 days prior to enrollment: 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 (New York Heart Association \[NYHA\] 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 absolute neutrophil count (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 10\^9/L (≤ 30 x 10\^9/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 glomerular filtration rate (GFR) less than 30 mL/min/1.73 m\^2 (per the Chronic Kidney Disease Epidemiology Collaboration formula) within 21 days prior to enrollment.

Primary outcomes:
measure: Number of Participants Who Completed 12 Cycles of Treatment
timeFrame: 12 cycles (each cycle is 28 days)
measure: Percentage of Expected Dose of Carfilzomib Received in Cycles 1 to 12
timeFrame: Up to 12 cycles (each cycle is 28 days)
measure: Relative Dose Intensity of Carfilzomib in Cycles 1 to 12
timeFrame: Up to 12 Cycles (each cycle is 28 days)
measure: Number of Participants With Carfilzomib Dose Modifications During Cycles 1 to 12
timeFrame: Cycles 1 - 12 (each cycle is 28 days)
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: From the first dose of study drug until 30 days after the last dose (12 months)
Secondary outcomes:
measure: Percentage of Expected Dose of Carfilzomib Received in Cycles 1 to 6 and 7 to 12
timeFrame: Cycles 1-6 and 7-12 (each cycle is 28 days)
measure: Relative Dose Intensity of Carfilzomib in Cycles 1 to 6 and 7 to 12
timeFrame: Cycles 1 - 6 and 7 - 12 (each cycle is 28 days)
measure: Number of Participants With Carfilzomib Dose Modifications During Cycles 1 to 6
timeFrame: Cycles 1 - 6 (each cycle is 28 days)
measure: Number of Participants With Carfilzomib Dose Modifications During Cycles 7 to 12
timeFrame: Cycles 7 - 12 (each cycle is 28 days)
measure: Number of Participants Who Discontinued Carfilzomib in Cycles 1 to 6 and 7 to 12
timeFrame: Cycles 1 - 6 and 7 - 12 (each cycle is 28 days)
measure: Change From Baseline to Last Cycle of Treatment in European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ)-Core 30 (C30)
timeFrame: Baseline (cycle 1 day 1) to cycle 12 day 1
measure: Change From Baseline in Average EORTC QLQ-C30 Scores During Cycles 2 to 6 in Participants Who Completed 12 Cycles of Treatment
timeFrame: Baseline (cycle 1 day 1) and cycles 2 - 6
measure: Change From Cycle 7 Day 1 in Average EORTC QLQ-C30 Scores During Cycles 8 to 12 in Participants Who Completed 12 Cycles of Treatment
timeFrame: Cycle 7 day 1 and cycles 8 - 12
measure: Change From Baseline to Last Cycle of Treatment in EORTC QLQ Multiple Myeloma Module (MY-20) Scores
timeFrame: Baseline (cycle 1 day 1) and cycle 12 day 1
measure: Change From Baseline in Average EORTC QLQ-MY20 Scores During Cycles 2 to 6 in Participants Who Completed 12 Cycles of Treatment
timeFrame: Baseline (cycle 1 day 1) and cycles 2 - 6
measure: Change From Cycle 7 Day 1 in Average EORTC QLQ-MY20 Scores Over Cycles 8 to 12 in Participants Who Completed 12 Cycles of Treatment
timeFrame: Cycle 7 day 1 and cycles 8 - 12
measure: Overall Response Rate (ORR)
timeFrame: Disease assessments were performed every 28 days up to 12 months from enrollment.
measure: Overall Response Rate (ORR) After 6 Cycles
timeFrame: Disease assessments were performed every 28 days up to 6 cycles of treatment (each cycle was 28 days)
measure: Overall Response Rate (ORR) by Prior Lines of Therapy
timeFrame: Disease assessments were performed every 28 days up to 12 months from enrollment.
measure: Percentage of Participants With Progression-free Survival (PFS) Events at 12 Months
timeFrame: 12 months
measure: Percentage of Participants With PFS Events by Prior Lines of Therapy
timeFrame: Disease assessments were performed every 28 days up to 12 months from enrollment.
Other outcomes:
Locations:
city: Palm Springs
country: United States
facility: Research Site
state: California
city: Riverside
country: United States
facility: Research Site
state: California
city: Glenwood Springs
country: United States
facility: Research Site
state: Colorado
city: Boynton Beach
country: United States
facility: Research Site
state: Florida
city: Orange City
country: United States
facility: Research Site
state: Florida
city: Pensacola
country: United States
facility: Research Site
state: Florida
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: River Forest
country: United States
facility: Research Site
state: Illinois
city: Tinley Park
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Paducah
country: United States
facility: Research Site
state: Kentucky
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Midland
country: United States
facility: Research Site
state: Michigan
city: Jackson
country: United States
facility: Research Site
state: Mississippi
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Florham Park
country: United States
facility: Research Site
state: New Jersey
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Hendersonville
country: United States
facility: Research Site
state: North Carolina
city: Pinehurst
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Zanesville
country: United States
facility: Research Site
state: Ohio
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Rock Hill
country: United States
facility: Research Site
state: South Carolina
city: Corpus Christi
country: United States
facility: Research Site
state: Texas
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Ogden
country: United States
facility: Research Site
state: Utah
city: Fredericksburg
country: United States
facility: Research Site
state: Virginia
city: Yakima
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: