Carfilzomib With Bendamustine and Dexamethasone in Multiple Myeloma

NCT ID: NCT02002598

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2023-07-01

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).

Detailed Description

Multiple myeloma (MM) is a malignant plasma cell disorder resulting in approximately 11,000 deaths in the United States each year. It is estimated that between 60,000-80,000 people are currently under treatment for refractory or relapsed MM. Prognosis and survival have improved over the last 20 years, but the disease is still universally fatal despite efforts to develop new and more effective chemotherapeutic regimens. Therefore, new regimens need to be developed for patients prior to peripheral blood stem cell transplant and for those unable to tolerate the toxicity of transplant.

An IRB-approved long-term retrospective chart review study (IRB-AAAU4389) was conducted to collect data for Outcome Measures relating to long-term analysis (up to 6.5 years).

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CFZ with bendamustine and dexamethasone

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.

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: 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

Carfilzomib

Intervention Type: 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

Dexamethasone

Intervention Type: 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.

Interventions

Bendamustine

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

Intervention Type: DRUG

Carfilzomib

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

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

Other Intervention Names

Treanda; Kyprolis; CFZ; Decadron; Dexamethasone Intensol; Dexpak Taperpak

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years.

2. Life expectancy ≥ 3 months.

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

4. Adequate hepatic function.

5. Sufficient Absolute neutrophil count (ANC) within 14 days prior to randomization.

6. Sufficient Hemoglobin within 14 days prior to randomization (subjects may be receiving red blood cell (RBC) transfusions in accordance with institutional guidelines).

7. Sufficient platelet count 14 days prior to randomization.

8. Creatinine Clearance ≥ 30 mL/minute within 7 days prior to randomization.

9. Left Ventricular Ejection Fraction ≥ 40%.

10. Written informed consent in accordance with federal, local, and institutional guidelines.

11. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.

12. Male subjects must agree to practice contraception.

13. Patients must have histologically or cytologically confirmed symptomatic multiple myeloma (MM). Patients should not have previously been treated.

14. Prior kyphoplasty, vertebroplasty, local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture) are permitted.

15. Patients are allowed up to two cycles of high dose steroids if needed for symptomatic disease before study enrollment.

Exclusion Criteria

1. 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).

2. 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.

3. Patients with non-measurable Multiple Myeloma or primary plasma cell leukemia.

4. Pregnant or lactating females.

5. Major surgery within 21 days prior to enrollment.

6. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment.

7. Known human immunodeficiency virus (HIV) infection.

8. Known active hepatitis B or C infection.

9. Unstable angina or myocardial infarction within 4 months prior to enrollment.

10. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.

11. Uncontrolled, non-hematologic malignancy requiring active treatment.

12. 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.

13. Significant neuropathy within 14 days prior to randomization.

14. Known history of allergy to Captisol, or to other agents in the study.

15. 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.

16. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment.

17. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Suzanne Lentzsch, MD

OTHER

Sponsor Role: lead

Responsible Party

Suzanne Lentzsch, MD

Professor of Clinical Medicine, Dept of Medical Hematology & Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Suzanne Lentzsch, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Irving Medical Center

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AAAJ2359

Identifier Type: -

Identifier Source: org_study_id