Study of Carfilzomib in Combination w/Dexamethasone in Patients w/Newly Diagnosed Multiple Myeloma

NCT01969565 | Terminated Phase 2 Results DMC

• 2 other identifiers: IRB00060113ISTCAR511
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of increasing doses of carfilzomib in combination with dexamethasone

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Tolerability and Safety of Increasing Doses of Carfilzomib in Combination With Dexamethasone.

  Adverse events will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The results will be tabulated to examine their frequency, organ systems affected, and relationship to study treatment. The results of laboratory assessments will be evaluated similarly.

  24 months

• Patients With ≥ VGPR (Very Good Partial Response)

  VGPR will be estimated based on the crude proportion of subjects whose best response is Stringent Complete Response (sCR), Complete Response (CR), and VGPR.

  4 months-8 months

Secondary Outcomes (1)

• Overall Response Rate (ORR), Defined as sCR, CR, Very Good Partial Response (VGPR), and PR at 4 Cycles

  4 months

Study Arms (1)

Carfilzomib in combination with dexamethasone

EXPERIMENTAL

Carfilzomib will be administered at a dose of 20 mg/m², with a dose escalation to 36 mg/m² after Days 1 and 2 of Cycle 1 in level 1; and at a dose of 20 mg/m², with a dose escalation to 45 mg/m² after Days 1 and 2 of Cycle 1 in level 2 in subjects with multiple myeloma who are newly diagnosed and treatment naïve. Dexamethasone will be given as a fixed dose of 20 mg PO/IV (1, 2, 8, 9, 15, 16, 22, and 23) for cycles 1 to 4 and for subsequent cycles.

Drug: Carfilzomib; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Also known as: Kyprolis

Carfilzomib in combination with dexamethasone

Dexamethasone DRUG

Also known as: Decadron

Carfilzomib in combination with dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have newly diagnosed multiple myeloma immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin E (IgE) or immunoglobulin D (IgD) by the International Myeloma Foundation (IMF) 2003 Diagnostic Criteria
• Subjects must be treatment naïve.
• Patient must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma.
• Prior treatment of hypercalcemia or spinal cord compression with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period).
• Patients treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, are eligible.
• One week must have lapsed since last date of radiotherapy, which is recommended to be a limited field.
• Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and one week have passed since the last date of therapy.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment.
• Age 18 years at the time of signing Informed Consent.
• Life expectancy of more than three months.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 or Karnofsky performance status of ≥ 60.
• Subject must be able to adhere to the study visit schedule and other protocol requirements.
• Written informed consent in accordance with federal, local, and institutional guidelines.
• Female subjects of child-bearing potential must have a negative serum pregnancy test within seven days of the first dose and agree to use dual methods of contraception during and for 3 months following last dose of drug.

You may not qualify if:

• Patient has \> Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment.
• Renal insufficiency as measured by calculated creatinine clearance \< 15 mL/min by Cockroft-Gault formula.
• Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count 50,000 cells/mm³).
• Subjects with an absolute neutrophil count (ANC) \< 1000 cells/mm³. Growth factors may not be used to meet ANC eligibility criteria.
• Total bilirubin \> 2.0 mg/dL or bilirubin ≥ 2 x upper limit of normal (ULN).
• Subjects with a hemoglobin \< 8.0 g/dL (Transfusion are permitted).
• Alanine aminotransferase (ALT) (SGPT) \> 2.5 x ULN.
• Aspartate aminotransferase (AST) ≥ 2.5 x ULN.
• Major surgery within three weeks of starting study drug (Cycle 1 Day 1).
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• Clinically relevant active infection requiring either oral or intravenous antibiotics or antifungal agents.
• Serious co-morbid medical conditions such as chronic obstructive or chronic restrictive pulmonary disease, and cirrhosis.
• Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study.
• Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or if the expected survival from other malignancy is less than 90% at 5 years.
• Uncontrolled diabetes mellitus (Fasting Blood Sugar \> 400 despite medical treatment).

Sponsors & Collaborators

• Emory University: lead
• Onyx Therapeutics, Inc.: collaborator

Study Sites (1)

Winship Cancer Institute-Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Limitations and Caveats

One patient consented but withdrew prior to beginning treatment.

Results Point of Contact

• Title: Jonathan Kaufman, MD
• Organization: Emory University

jlkaufm@emory.edu

404-778-1900

Study Officials

• Jonathan Kaufman, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 4, 2013
• First Posted: October 25, 2013
• Study Start: August 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: November 24, 2017
• Results First Posted: November 4, 2015

Record last verified: 2017-10

Locations

US (1)