Clinical trial NCT02002598: Carfilzomib With Bendamustine and Dexamethasone in Multiple Myeloma
Official title: Phase I/II Study of Carfilzomib in Combination With Bendamustine and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2013-12-06
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Carfilzomib in Combination With Bendamustine and Dexamethasone
timeFrame: 6 months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 2 years
measure: Time to Next Treatment (TTNT)
timeFrame: Up to 6.5 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 6.5 Years
measure: Time to Best Response
timeFrame: 2 years
measure: Overall Survival (OS) Rate
timeFrame: Up to 6.5 Years
measure: Number of Adverse Events (AEs)
timeFrame: 30 Days Post Last Dose, Up to approximately 9 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Suzanne Lentzsch, MD
role: PRINCIPAL_INVESTIGATOR
References: