- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01246063
Carfilzomib, Pegylated Liposomal Doxorubicin Hydrochloride, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
A Phase I/II Trial of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically confirmed diagnosis of multiple myeloma with a measurable disease parameter at time of screening; a measurable disease parameter is defined as one or more of the following:
- Serum monoclonal protein >= 0.5 g/dl
- 24 hour urine monoclonal protein >= 0.2 g/24 hour
- Serum free light chain ratio > 5 x normal ratio with an absolute difference of 10mg/dl between the involved and uninvolved free light chain
- Soft tissue plasmacytoma >= 2 cm measurable by either physical examination and/or applicable radiographs (e.g. magnetic resonance imaging [MRI], computed tomography [CT], etc)
- Bone Marrow Plasma Cells >= 30%
- Documentation of at least one line of prior myeloma therapy now with relapsed or refractory disease requiring re-treatment
- At least 18 years of age at the time of signing the informed consent.
- Performance status of Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky >= 60%; participants with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible
Required laboratory values
- Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 2.5 x the upper limit of the institutional normal value (ULN)
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Absolute neutrophil count (ANC) >= 1,000
- Hemoglobin >= 8 g/dl
- Platelets >= 50,000
- Creatinine clearance > 15 ml/minute using Cockcroft-Gault formula
- For those participants receiving warfarin (Coumadin), unfractionated heparin, or low-molecular weight heparin therapy, the applicable coagulation parameter that is being monitored must be within the accepted therapeutic ranges for those indications
- Transfusions and/or growth factor dependent participants are not excluded if the above parameters can be achieved with such support
- Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on study drug and for 3 months after discontinuation from study drug, and must agree to use adequate contraception including hormonal contraception, (i.e. birth control pills, etc), barrier method contraception (i.e. condoms), or abstinence during that time frame; FCBP must agree to regular pregnancy testing during this timeframe; inclusion of FCBP requires two negative pregnancy tests prior to enrollment. All women, regardless of age, should be considered FCBP unless they are surgically sterile (post hysterectomy, post bilateral oophorectomy, etc) or have been naturally post menopausal for >= 24 consecutive months
- Men engaging in sexual intercourse with a FCBP must agree to use adequate contraception including hormonal contraception, (i.e. birth control pills, etc), barrier method contraception (i.e. condoms), or abstinence while on study drug and for 3 months after discontinuation from study drug
- Ability to understand and willing to sign a written informed consent document
Exclusion Criteria:
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma Cell Leukemia
- Waldenstrom's macroglobulinemia
- Pregnant or lactating females
- Use of any anti-myeloma drug therapy within 14 days of initiation of study drug treatment excluding corticosteroids if given for an indication other than myeloma; bisphosphonates are not considered anti-myeloma drugs
- Participation in an investigational therapeutic study within 14 days of initiation of study drug treatment
- Radiotherapy to multiple sites or immunotherapy within 14 days of initiation of study drug treatment (localized radiotherapy to a single site at least 7 days before start is permissible)
- Major surgery within 14 days of initiation of study drug treatment
- Participants in whom the required program of oral (PO) and IV fluid hydration is contraindicated
- Prior history of a hypersensitivity reaction to PLD, doxorubicin, bortezomib, carfilzomib, or liposomal drug formulations other than PLD; history of reactions to liposomal drug formulations other than PLD should be evaluated individually and if their reactions were felt to have been due to the encapsulated agent, rather than the liposomal component itself they should be excluded at the discretion of the investigators
- Participants who are known to have active hepatitis A, B, or C viral infection may not participate in this study; active disease is defined as participants with a known viral hepatitis whose liver function tests are elevated
- Known human immunodeficiency virus (HIV)-seropositive and are taking anti-retrovirals may not participate in this study; participants who are HIV-seropositive and not on anti-retroviral therapy and who otherwise meet the inclusion/exclusion criteria will be eligible for the study
Compromised cardiovascular function defined as any of the following:
- Electrocardiogram (EKG) evidence of acute ischemia
- EKG evidence of medically significant conduction system abnormalities
- History of myocardial infarction within the last 6 months
- Unstable angina pectoris or cardiac arrhythmia
- History of Class 3 or Class 4 New York Heart Association Congestive Heart Failure within 6 months of enrollment on study
- Left ventricular ejection fraction (LVEF) < 45% by either echocardiography or radionuclide-based multiple gated acquisition (Echo or MUGA)
- Uncontrolled concurrent illness including: other hematologic or non-hematologic malignancy, active infection, or uncontrolled diabetes
- Any significant psychological, medical, or surgical condition thought to compromise the participant, the study, or prevent informed consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)
Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1.
Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6.
Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+.
PLD IV (30 mg/m^2)D8 C1-6.
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Other Names:
Other Names:
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Experimental: Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)
Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 1: Carfilzomib IV (1 dose level above MTD) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (1 dose level above MTD) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (1 dose level above MTD) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib. Dose Level 2: Carfilzomib IV (2 dose levels above MTD) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (2 dose levels above MTD) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (2 dose levels above MTD) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib. |
Other Names:
Other Names:
|
Experimental: Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)
Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1.
Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6.
Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+.
PLD IV (30 mg/m^2)D8 C1-6.
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Other Names:
Other Names:
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Experimental: Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)
Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1.
Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6.
Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+.
PLD IV (30 mg/m^2)D8 C1-6.
|
Other Names:
Other Names:
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Experimental: Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)
Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6.
Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles.
PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle.
Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
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Other Names:
Other Names:
Other Names:
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Experimental: Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)
Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6.
Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles.
PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle.
Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
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Other Names:
Other Names:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) of Carfilzomib and Pegylated Liposomal Doxorubicin (Phase I - Part 1).
Time Frame: 28 days (completion of first cycle of all Phase I - Part 1 patients)
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28 days (completion of first cycle of all Phase I - Part 1 patients)
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Maximum Tolerated Dose (MTD) of Carfilzomib and PLD (Phase I - Part 2).
Time Frame: 28 days (completion of first cycle of all Phase I - Part 2 patients)
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-MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1.
If DLT is observed, MTD will be the next lower dose level.
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28 days (completion of first cycle of all Phase I - Part 2 patients)
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Maximum Tolerated Dose (MTD) of Dexamethasone (Phase I - Part 2).
Time Frame: 28 days (completion of first cycle of all Phase I - Part 2 patients)
|
-MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1.
If DLT is observed, MTD will be the next lower dose level.
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28 days (completion of first cycle of all Phase I - Part 2 patients)
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Phase 2 - Efficacy of Carfilzomib in Combination With PLD and Dexamethasone as Measured by the Percentage of Participants With Confirmed Tumor Responses
Time Frame: Completion of treatment (median number of cycles was 9.5 (range 1-34))
|
-A confirmed response is defined to be a complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG Criteria.
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Completion of treatment (median number of cycles was 9.5 (range 1-34))
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Phase 2 - Toxicity of Carfilzomib in Combination With PLD and Dexamethasone as Measured by Number of Participants Who Experience Grade 3/4 Toxicity
Time Frame: Through 30 days after completion of treatment (median number of cycles was 9.5 (range 1-34))
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Through 30 days after completion of treatment (median number of cycles was 9.5 (range 1-34))
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Overall Survival
Time Frame: Completion of follow-up (median of 23.3 months)
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Completion of follow-up (median of 23.3 months)
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Progression-free Survival Time (Phase 2 Only)
Time Frame: Through completion of follow-up (median follow-up was 23.3 months)
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-Progression per IMWG Criteria
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Through completion of follow-up (median follow-up was 23.3 months)
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Median Duration of Overall Response
Time Frame: Through completion of follow-up (median follow-up was 23.3 months)
|
|
Through completion of follow-up (median follow-up was 23.3 months)
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Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Dexamethasone
- Doxorubicin
- Liposomal doxorubicin
Other Study ID Numbers
- 201102043
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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