Carfilzomib and Lenalidomide With Dexamethasone Combination in Newly Diagnosed, Previously Untreated Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Onyx Therapeutics, Inc.
Celgene Corporation
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01029054
First received: December 8, 2009
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

This study is designed to evaluate the safety and to determine the maximum tolerated dose of carfilzomib + lenalidomide in combination with dexamethasone in newly diagnosed Multiple Myeloma patients who have not received treatment.


Condition Intervention Phase
Multiple Myeloma
Drug: carfilzomib, lenalidomide plus dexamethasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: Multicenter, Open-label, Single-arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment w/ Carfilzomib, Lenalidomide (Revlimid®) and Dexamethasone (CRD) in Subjects w/ Newly Diagnosed, Previously Untreated Multiple Myeloma Requiring Systemic Chemotherapy

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • • Phase 1b - Safety and MTD of the combination therapy • Phase 2 - Week 16 (end of cycle 4) complete and near complete response rate (sCR, CR, CR) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • • Determining the overall response rate • Time on Study (TOS), Duration of response (DOR), progression free survival (PFS), time to progression (TTP) and overall survival(OS)distributions [ Time Frame: indefinitely ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: September 2009
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: carfilzomib, lenalidomide w/dexamethasone

Phase I: carfilzomib will be taken with a combination of lenalidomide plus dexamethasone in a series of escalating dosages to determine the maximum tolerated dose level

Phase II: carfilzomib will be given at the MTD established in the Phase I portion of the study

Drug: carfilzomib, lenalidomide plus dexamethasone

Phase I: Carfilzomib will be administered at the dosage assigned for the subject's cohort as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance).

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone 40 mg will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

Drug: carfilzomib, lenalidomide plus dexamethasone

Phase II: Carfilzomib will be administered at the Maximum Tolerated Dose (MTD) established in Phase I as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance).

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push on Days 1, 8, 15, and 22 as follows: Cycles 1-4: 40 mg; Cycles 5-8: 20 mg; and Cycles 9 and higher: 10 mg.


Detailed Description:

During the Phase I portion of this clinical trial, the dose of Revlimid® and carfilzomib will be increased until the best and safest amount (or dose) is identified in combination with standard doses of Revlimid® and dexamethasone. "Investigational" means that the drug combination is still being studied and that research doctors are trying to find out more about it such as the safest dose to use, the side effects it may cause and how effective the Revlimid® and carfilzomib and dexamethasone investigational combination is for treating newly diagnosed multiple myeloma. In this clinical trial we are looking for the highest dose of the combination that can be given safely and see how well it works as a combination in newly diagnosed patients.

The drug, carfilzomib, has not yet been approved by the FDA (U.S. Food and Drug Administration). Revlimid® and Dexamethasone have been approved by the FDA. The drugs have not been approved in this combination for use for your type of cancer or any other type of cancer. Carfilzomib is being researched to treat multiple myeloma. Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma. Revlimid® is currently approved by the US FDA in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.

After the Phase I clinical trial defines the safest doses of Revlimid® and carfilzomib and dexamethasone that can be taken together, the research study will move on to its second portion, a Phase II clinical trial. The Phase II portion of the clinical trial will test the clinical effectiveness of the best dose combination of the three drugs.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Newly diagnosed, histologically confirmed, previously untreated Stage I, II, or III multiple myeloma requiring systemic chemotherapy
  2. Diagnosis of symptomatic multiple myeloma per IMWG uniform criteria within the past 90 days
  3. Measurable disease, per IMWG criteria (>= one of the following) within the past 4 weeks:

    • Monoclonal protein >= 0.5 g/dL by serum protein electrophoresis
    • Monoclonal light chain >= 200 mg by 24-hour urine protein electrophoresis
    • If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable
  4. Life expectancy > 3 months
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  6. Adequate hepatic function, with bilirubin < 1.5 x the ULN, and AST and ALT < 2.5 x ULN
  7. Absolute neutrophil count (ANC) >=1.0 x 109/L, hemoglobin >= 8 g/dL, platelet count >= 75 x 109/L
  8. Calculated creatinine clearance (by Cockroft-Gault) >= 60 ml/min
  9. Written informed consent in accordance with federal, local, and institutional guidelines
  10. Subjects must agree to adhere to all study requirements, including birth control measures and pregnancy testing, visit schedule, outpatient treatment, required concomitant medications, and laboratory monitoring
  11. Must be able to take either 81 mg or 325 mg aspirin daily as prophylactic anticoagulation

Exclusion Criteria

  1. Non-secretory or hyposecretory multiple myeloma, defined as <0.5 g/dL M-protein in serum, <200 mg/24 hr urine M-protein, or disease only measured by serum free light chain
  2. POEMS syndrome
  3. Plasma cell leukemia
  4. Waldenström's macroglobulinemia or IgM myeloma
  5. Radiotherapy to multiple sites or immunotherapy within 2 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
  6. 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 or aggressively progressing myeloma with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period)
    • Bisphosphonates are permitted
  7. Participation in an investigational therapeutic study within 3 weeks or within 5 drug halflives (t1/2) prior to first dose, whichever time is greater
  8. Pregnant or lactating females
  9. History of allergy to mannitol
  10. Major surgery within 3 weeks prior to first dose
  11. Myocardial infarction within 3 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  12. Uncontrolled hypertension or diabetes
  13. Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
  14. Known or suspected HIV infection, known HIV seropositivity
  15. Active hepatitis infection
  16. Non-hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone
  17. Any 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
  18. Significant neuropathy (Grade >2) at the time of the first dose and/or within 14 days before enrollment
  19. Contraindication to any of the required concomitant drugs
  20. Subjects in whom the required program of PO and IV fluid hydration is contraindicated
  21. Subjects with known or suspected amyloidosis of any organ
  22. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01029054

Locations
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Mt. Sinai Medical Center
New York, New York, United States, 10029
Sponsors and Collaborators
University of Michigan Cancer Center
Onyx Therapeutics, Inc.
Celgene Corporation
Investigators
Principal Investigator: Mark Kaminski, M.D. University of Michigan Cancer Center
  More Information

No publications provided by University of Michigan Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01029054     History of Changes
Other Study ID Numbers: UMCC 2009.056, HUM30396
Study First Received: December 8, 2009
Last Updated: October 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan Cancer Center:
Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 29, 2014