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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Multiple Myeloma

Thank you

Trial Information

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

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.

Inclusion 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

- 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

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

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

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

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

- 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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Outcome Measure:

• 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)

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Mark Kaminski, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Michigan Cancer Center


United States: Food and Drug Administration

Study ID:

UMCC 2009.056



Start Date:

September 2009

Completion Date:

June 2015

Related Keywords:

  • Multiple Myeloma
  • Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
Washington University School of Medicine Saint Louis, Missouri  63110
Hackensack University Medical Center Hackensack, New Jersey  07601
Mt. Sinai Medical Center New York, New York  10029