Carfilzomib With Bendamustine and Dexamethasone in Multiple Myeloma

NCT02002598 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAJ2359
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to define dose-limiting toxicity and determine preliminary evidence of efficacy of carfilzomib (CFZ) in combination with bendamustine and dexamethasone for patients with newly diagnosed multiple myeloma (MM).

Conditions

Multiple Myeloma

Keywords

Newly diagnosed; multiple myeloma; myeloma; bendamustine; Treanda; carfilzomib; dexamethasone; phase I; phase II; dose escalation; transplant; non-transplant; plasma cell; Kyprolis

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Carfilzomib in Combination With Bendamustine and Dexamethasone

  MTD defined as the highest dose at which ≤20% of participants experience dose-limiting toxicity (DLT), to define the recommended phase II dose. DLT were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute version 4.0. An AE was considered a DLT if it occurred in cycle 1, was deemed related to study treatment, and was one of peripheral neuropathy ≥grade 2, any non-hematologic AE ≥ grade 3, neutropenia grade 4 lasting ≥7 days or with fever, thrombocytopenia grade 4 lasting ≥7 days or with bleeding, or any AE requiring a dose reduction during cycle 1 or a delay in the start of cycle 2.

  6 months

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  2 years

• Time to Next Treatment (TTNT)

  Up to 6.5 years

• Progression Free Survival (PFS)

  Up to 6.5 Years

• Time to Best Response

  2 years

• Overall Survival (OS) Rate

  Up to 6.5 Years

Study Arms (1)

CFZ with bendamustine and dexamethasone

EXPERIMENTAL

Subjects will receive Carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days with dose escalation from 27, 36, 45 to 56 mg/ m2 . No matter what target dose the subject will receive, days 1 and 2 doses in the first cycle will always be 20 mg/m2, followed by target dose for all subsequent dates and cycles. Bendamustine will be given IV on days 1 and 2 with dose escalation up to 90 mg/m2 and dexamethasone 20 mg orally or intravenously on 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle. Study treatment will be given until 8 cycles of treatment are completed or until disease progression, whichever comes first.

Drug: Bendamustine; Drug: Carfilzomib; Drug: Dexamethasone

Interventions

Bendamustine DRUG

Bendamustine will be administered IV on days 1 and 2 with dose escalation up to 90 mg/m2 of each 28-day cycle. Dose escalation is as follows: -1 \| 60 mg/m2 1. \| 70 mg/m2 2. \| 70 mg/m2 3. \| 90 mg/m2 4. \| 90mg/m2 5. \| 90 mg/m2

Also known as: Treanda

CFZ with bendamustine and dexamethasone

Carfilzomib DRUG

Carfilzomib will be administered IV on Days 1, 2, 8, 9, 15, and 16 every 28 days. Dose Escalation is as follows: -1 \| 27 mg/m2 1. \| 27 mg/m2 2. \| 36 mg/m2 3. \| 36 mg/m2 4. \| 45 mg/m2 5. \| 56 mg/m2

Also known as: Kyprolis, CFZ

CFZ with bendamustine and dexamethasone

Dexamethasone DRUG

Dexamethasone will be administered PO or IV, 20 mg, on 1, 2, 8, 9, 15, 16 and 22, 23 of each 28-day cycle.

Also known as: Decadron, Dexamethasone Intensol, Dexpak Taperpak

CFZ with bendamustine and dexamethasone

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Life expectancy ≥ 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Adequate hepatic function.
• Sufficient Absolute neutrophil count (ANC) within 14 days prior to randomization.
• Sufficient Hemoglobin within 14 days prior to randomization (subjects may be receiving red blood cell (RBC) transfusions in accordance with institutional guidelines).
• Sufficient platelet count 14 days prior to randomization.
• Creatinine Clearance ≥ 30 mL/minute within 7 days prior to randomization.
• Left Ventricular Ejection Fraction ≥ 40%.
• Written informed consent in accordance with federal, local, and institutional guidelines.
• Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.
• Male subjects must agree to practice contraception.
• Patients must have histologically or cytologically confirmed symptomatic multiple myeloma (MM). Patients should not have previously been treated.
• Prior kyphoplasty, vertebroplasty, local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture) are permitted.
• Patients are allowed up to two cycles of high dose steroids if needed for symptomatic disease before study enrollment.

You may not qualify if:

• Patients who have had chemotherapy for Multiple Myeloma. Exception: local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture).
• Patients currently receiving high dose systemic steroids for treatment of Multiple Myeloma in excess of 320mg total dose of dexamethasone or equivalent, patients who received an investigational agent within 5 half-lives of the agent.
• Patients with non-measurable Multiple Myeloma or primary plasma cell leukemia.
• Pregnant or lactating females.
• Major surgery within 21 days prior to enrollment.
• Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment.
• Known human immunodeficiency virus (HIV) infection.
• Known active hepatitis B or C infection.
• Unstable angina or myocardial infarction within 4 months prior to enrollment.
• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.
• Uncontrolled, non-hematologic malignancy requiring active treatment.
• Patients with known brain metastases (treated or not) will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Significant neuropathy within 14 days prior to randomization.
• Known history of allergy to Captisol, or to other agents in the study.
• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.

Sponsors & Collaborators

• Suzanne Lentzsch, MD: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bendamustine Hydrochloride; carfilzomib; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

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)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Limitations and Caveats

The limitations of this study include a small sample size, failure to complete planned accrual, and lack of high cytogenetic risk patients.

Results Point of Contact

• Title: Suzanne Lentzsch, MD
• Organization: Columbia University

sl3440@cumc.columbia.edu

646-317-4840

Study Officials

• Suzanne Lentzsch, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical Medicine, Dept of Medical Hematology & Oncology

Study Record Dates

• First Submitted: December 2, 2013
• First Posted: December 6, 2013
• Study Start: November 1, 2013
• Primary Completion: March 1, 2019
• Study Completion: July 1, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)