Trial Title:
Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Therapy for Subjects With Multiple Myeloma
NCT ID:
NCT01559935
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Clarithromycin
Dexamethasone
Dexamethasone acetate
Lenalidomide
BB 1101
Conditions: Keywords:
Multiple Myeloma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
carfilzomib
Description:
45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles.
Arm group label:
Car-BiRD Therapy
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving
carfilzomib.
Arm group label:
Car-BiRD Therapy
Other name:
DECADRON®
Intervention type:
Drug
Intervention name:
Clarithromycin
Description:
500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib
treatment has been completed.
Arm group label:
Car-BiRD Therapy
Other name:
Biaxin
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after
carfilzomib treatment has been completed.
Arm group label:
Car-BiRD Therapy
Other name:
Revlimid
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins
after carfilzomib treatment has been completed.
Arm group label:
Car-BiRD Therapy
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after
BiRD treatment has been completed.
Arm group label:
Car-BiRD Therapy
Other name:
Revlimid
Summary:
The purpose of this study is to evaluate the safety and effectiveness of an
investigational new drug called carfilzomib, in combination with dexamethasone in
subjects with newly diagnosed multiple myeloma followed by treatment with a combination
of drugs clarithromycin (Biaxin®), lenalidomide (Revlimid®) and dexamethasone (Decadron®)
[BiRD] then lenalidomide alone.
Detailed description:
While new anti-myeloma therapies such as bortezomib and immunomodulatory drugs have been
developed, multiple myeloma remains an incurable malignancy. Given that obtaining a
complete remission (CR) with therapy will allow patients with newly diagnosed multiple
myeloma to enjoy a higher quality of life and longer duration of freedom from disease
symptoms, finding an optimally effective and well-tolerated regimen is imperative.
The robust overall response rate of 91% with the BiRD regimen for patients with newly
diagnosed multiple myeloma is encouraging and we believe that by adding carfilzomib the
overall response rate and CR rate can be improved. As carfilzomib has proven efficacy in
myeloma and in patient's who have relapsed on bortezomib, we anticipate that it will
synergize with the previous BiRD regimen to induce greater reduction of tumor burden
overall.
The primary endpoints include best response rate, toxicities, progression free survival,
event free survival, and overall survival. In those patients who are eligible for
autologous stem cell transplantation, we will also study the effect of carfilzomib on CD
34+ stem cell yield following mobilization.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Subject must voluntarily sign and understand written informed consent.
- Subject is ≥ 18 years at the time of signing the consent form.
- Subject has histologically confirmed multiple myeloma that has never before been
treated.
- Subject had no anti-myeloma therapy within 14 days prior to initiation of study
treatment except for corticosteroids with a maximum allowed dosage equivalent to
three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients may
have received prior adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic
acid) as routine care, or radiation therapy as palliation for pain and/or spinal
cord compression.
- Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >
10 mg/dL involved serum free light chain (either kappa or lambda) provided that the
serum free light chain ratio is abnormal, > 0.2 g/24 hrs urinary M-protein
excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension
as measured by either CT scanning or MRI.
- Subject has a Karnofsky performance status ≥ 60% (> 50% if due to bony involvement
of myeloma (see Appendix VI).
- Subject is able to take prophylactic anticoagulation as detailed in section 9.1
(patients intolerant to aspirin may use warfarin or low molecular weight heparin).
- Subject is registered into the mandatory RevAssist® program, and is willing and able
to comply with the requirements of RevAssist® program.
- If subject is a female of childbearing potential (FCBP),† she must have a negative
serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 -
14 days prior to and again within 24 hours of prescribing lenalidomide
(prescriptions must be filled within 7 days) and must either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
control, one highly effective method and one additional effective method AT THE SAME
TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree
to ongoing pregnancy testing. Men must agree to use a latex condom during sexual
contact with females of child bearing potential even if they have had a successful
vasectomy.
- Subjects must meet the following laboratory parameters:
- Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L)
- Hemoglobin ≥ 7 g/dL
- Platelet count ≥ 30,000/mm3 (75 x 109/L)
- Serum SGOT/AST < 3.0 x upper limits of normal (ULN)
- Serum SGPT/ALT < 3.0 x upper limits of normal (ULN)
- Serum creatinine < 2.5 mg/dL (221 µmol/L)
- Serum total bilirubin < 2.0 mg/dL (34 µmol/L)
Exclusion Criteria:
- Subject has immeasurable MM (no measurable monoclonal protein, free light chains in
blood or urine, or measureable plasmacytoma on radiologic scanning).
- Subject has a prior history of other malignancies unless disease free for ≥ 5 years,
except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of
the cervix or breast, or localized prostate cancer with Gleason score < 7 with
stable prostate specific antigen (PSA) levels.
- Subject has had myocardial infarction within 6 months prior to enrollment , or
NYHA(New York Hospital Association) Class III or IV heart failure, Ejection Fraction
< 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias,
electrocardiographic evidence of acute ischemia or active conduction system
abnormalities.
- Female subject who is pregnant or lactating.
- Subject has known HIV infection
- Subject has known active hepatitis B or hepatitis C infection.
- Subject has active viral or bacterial infections or any coexisting medical problem
that would significantly increase the risks of this treatment program.
- Subject has known hypersensitivity to dexamethasone, clarithromycin, lenalidomide,
thalidomide, allopurinol, or carfilzomib.
- Subject has a history of thromboembolic event within the past 4 weeks prior to
enrollment.
- Subject has any clinically significant medical or psychiatric disease or condition
that, in the Investigator's opinion, may interfere with protocol adherence or a
subject's ability to give informed consent.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Weill Cornell Medical College
Address:
City:
New York
Zip:
10021
Country:
United States
Start date:
March 2012
Completion date:
March 2026
Lead sponsor:
Agency:
Weill Medical College of Cornell University
Agency class:
Other
Collaborator:
Agency:
Onyx Therapeutics, Inc.
Agency class:
Industry
Source:
Weill Medical College of Cornell University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01559935
