Study of Carfilzomib for Multiple Myeloma Patients Who Are Relapsed/Refractory to Bortezomib-containing Treatments

NCT01365559 | Completed Phase 1

• 1 other identifier: IST-CAR-516
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 9

Brief Summary

This is a phase I/II multicenter, open label, nonrandomized study for patients with Multiple Myeloma (MM) who will receive treatment with carfilzomib in place of bortezomib using the same bortezomib-containing combination regimen to which a MM patient has progressed while receiving. This study will enroll 45 patients total. These patients will be resistant to bortezomib as demonstrated by progressive disease while on bortezomib or have relapsed within 12 weeks of the last dose of bortezomib in a combination regimen. Patients will be sub-divided into 2 groups in this study, treatments containing (Group A) or not containing immunomodulatory drugs (IMiDs) (Group B). Thirty patient will be enrolled into Group A and 15 patients into Group B for a total of 45 patients. Patients must have received 4 doses of a minimum of 1.0 mg/m\^2 of bortezomib in no more than 4 weeks per cycle. Patients must have received at least one cycle meeting this definition and have shown progressive disease to be considered eligible. Patients who have been refractory to or relapsed within 12 weeks of the last dose of bortezomib in their most recent bortezomib-containing regimen that does not include either thalidomide or lenalidomide are eligible regardless of when patients received that regimen, as long as they meet the above criteria. Carfilzomib will subsequently replace bortezomib using the patient's most recent bortezomib-containing regimen to which the patient progressed while receiving. Patients will be eligible if they progressed from bortezomib with an alkylating agent (melphalan or cyclophosphamide), an anthracycline (doxorubicin or pegylated liposomal doxorubicin) and/or a glucocorticosteroid (prednisone, dexamethasone or medrol)and IMiD (thalidomide or lenalidomide). The study will consist of a screening period, followed by up to eight open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment cycle, a follow-up period and maintenance cycles of single agent carfilzomib. Patient who complete the combination treatment period without progressive disease will be eligible for maintenance therapy with single-agent carfilzomib. During maintenance therapy carfilzomib will be administered at the same dose given during the last cycle of combination treatment.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; carfilzomib; relapsed; refractory; bortezomib; Oncotherapeutics

Outcome Measures

Primary Outcomes (1)

• Establish MTD, determine DLT and to determine the efficacy as assessed by the overall response rate.

  Phase I: • To establish the maximum tolerated dose (MTD) and determine the dose limiting toxicities (DLT) following treatment. Phase II: • To determine the efficacy as assessed by the overall response rate \[CR + VGPR + PR + MR\] and the Time to Progression (TTP) of disease.

  Montly

Secondary Outcomes (1)

• To establish safety and efficacy following treatment.

  Montly

Study Arms (2)

Group A: Carfilzomib & Non-IMiD containing regimen

EXPERIMENTAL

Bortezomib is replaced with carfilzomib in a combined regimen identical to the patient's previous regimen. Regimen cannot include thalidomide or lenalidomide.

Drug: Group A: Carfilzomib & Non-IMiD Regimen

Group B: Carfilzomib & IMiD containing regimen.

EXPERIMENTAL

Bortezomib is replaced with carfilzomib in a regimen that includes IMiDs (lenalidomide or thalidomide). Thus, the regimen is carfilzomib in an IMiD-containing regimen.

Drug: Group B: Carfilzomib & IMiD containing regimen.

Interventions

Group A: Carfilzomib & Non-IMiD Regimen DRUG

Carfilzomib will be administered intravenously starting at a dose of 20 mg/m\^2 over 30 minutes for the first cycle and will then be increased to 27, 36 and 45 mg/m2 during cycles 2-4, respectively. Doses will be administered IV once daily on days 1, 2, 8, 9, 15, and 16 of each cycle. Cycles will be 28 days in length. Combination non-IMiD drug is dosed on the identical schedule and dosage as patient was in previous bortezomib containing regimen. Maintenance regimen maybe administered if patient does not progress while on study.

Group A: Carfilzomib & Non-IMiD containing regimen

Group B: Carfilzomib & IMiD containing regimen. DRUG

Carfilzomib will be administered intravenously starting at a dose of 20 mg/m\^2 over 30 minutes for the first cycle and will then be increased to 27, 36 and 45 mg/m2 during cycles 2-4, respectively. Doses will be administered IV once daily on days 1, 2, 8, 9, 15, and 16 of each cycle. Cycles will be 28 days in length. Combination IMiD drug is dosed on the identical schedule and dosage as patient was in previous bortezomib containing regimen. Maintenance regimen maybe administered if patient does not progress while on study.

Group B: Carfilzomib & IMiD containing regimen.

Eligibility Criteria

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

You may qualify if:

• Disease-related:
• Have a diagnosis of MM based on standard criteria
• Currently has MM with measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 gm/dL and/or urine monoclonal immunoglobulin amount of at least 200 mg/24 hours.
• Have relapsed within 12 weeks of receiving or is refractory to their most recent bortezomib-containing regimen as long as they meet the following criteria:
• Progressed from bortezomib-containing regimen either as a single agent or in combination with an alkylating agent (melphalan or cyclophosphamide), an anthracycline (doxorubicin or pegylated liposomal doxorubicin), IMiDs (thalidomide or lenalidomide), and/or a glucocorticosteroid (prednisone, dexamethasone or medrol)
• Bortezomib must have been administered at 4 doses of a minimum of 1.0 mg/m2 in no more than 28 days per cycle. Subjects must have received at least one cycle meeting this definition and have shown progressive disease to be considered eligible.
• Subject who have been refractory to their most recent bortezomib-containing regimen are eligible regardless of when the subject received that regimen, as long as they meet the above criteria and have been off the treatment for \> 3 weeks.
• Definition of refractory disease: patients who meet criteria for progressive disease while currently receiving treatment.
• Demographics:
• Age ≥ 18 years
• Life expectancy ≥ 3 months
• ECOG performance status 0-2 at study entry
• Laboratory tests (within 14 days prior to drug dosing on Cycle 1, Day 1)
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; if the bone marrow is extensively infiltrated (\> 70% plasma cells) then 1.0 x 109/L
• Hemoglobin ≥ 8 g/dL (subjects may be receiving red blood cell \[RBC\] transfusions in accordance with institutional guidelines)

You may not qualify if:

• Disease-related
• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes (POEMS) syndrome
• Plasma cell leukemia
• Severe hypercalcemia, i.e., serum calcium 12 mg/dL (3.0 mmol/L) corrected for albumin
• Received the following prior therapy:
• Chemotherapy within 21 days of enrollment (6 wks for nitrosoureas)
• Corticosteroids (\>10 mg/day prednisone or equivalent) within 21 days of enrollment
• Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic trioxide, or bortezomib within 21 days before enrollment
• Radiation therapy within 21 days before enrollment, receipt of localized radiation therapy does not preclude enrollment
• Use of any other experimental drug or therapy within 28 days of enrollment
• Concurrent Conditions
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• Unstable angina or myocardial infarction within 4 months prior to enrollment
• NYHA Class III or IV heart failure
• Uncontrolled angina

Sponsors & Collaborators

• Oncotherapeutics: lead
• Amgen: collaborator

Study Sites (9)

Pacific Oncology and Hematology

Encinitas, California, 92024, United States

Location

Pacific Cancer Care

Salinas, California, 93901, United States

Location

Central Coast Medical Oncology

Santa Maria, California, 93454, United States

Location

James R. Berenson, MD, Inc.

West Hollywood, California, 90069, United States

Location

Cancer Centers of America

Zion, Illinois, 60099, United States

Location

Franciscan St. Francis Health

Indianapolis, Indiana, 46237, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Family Cancer Center Foundation, Inc.

Memphis, Tennessee, 38119, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 233031, United States

Location

Related Publications (1)

• Berenson JR, Hilger JD, Yellin O, Dichmann R, Patel-Donnelly D, Boccia RV, Bessudo A, Stampleman L, Gravenor D, Eshaghian S, Nassir Y, Swift RA, Vescio RA. Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy. Leukemia. 2014 Jul;28(7):1529-36. doi: 10.1038/leu.2014.27. Epub 2014 Jan 16.

  PMID: 24429497 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• James R Berenson, MD

  James R. Berenson, MD., Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2011
• First Posted: June 3, 2011
• Study Start: May 2, 2011
• Primary Completion: June 13, 2014
• Study Completion: March 1, 2016
• Last Updated: March 5, 2018

Record last verified: 2018-03

Locations

US (9)