Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Therapy for Subjects With Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Weill Medical College of Cornell University
Sponsor:
Collaborator:
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01559935
First received: February 16, 2012
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: carfilzomib
Drug: Dexamethasone
Drug: Clarithromycin
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Sequential Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Therapy for Subjects With Newly Diagnosed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Response to Car-BiRD treatment. [ Time Frame: Up to 36 months. ] [ Designated as safety issue: No ]

    Response categories:

    Stringent Complete Response (sCR), Complete Remission(CR), Very Good Partial Remission(VGPR), Partial Remission (PR), Progressive Disease (PD), Stable Disease, Plateau.



Secondary Outcome Measures:
  • Event free survival [ Time Frame: From date of study enrollment until the date of first documented progression, assessed up to 36 months. ] [ Designated as safety issue: No ]
    an event is defined by coming off protocol for any reason, including progression of disease, lack of disease response, regimen intolerability, or death.


Estimated Enrollment: 57
Study Start Date: March 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Car-BiRD Therapy
Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD]
Drug: carfilzomib
45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles.
Drug: Dexamethasone
20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib.
Other Name: DECADRON®
Drug: Clarithromycin
500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.
Other Name: Biaxin
Drug: Lenalidomide
25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.
Other Name: Revlimid
Drug: Dexamethasone
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.
Drug: Lenalidomide
10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Other Name: Revlimid

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01559935

Contacts
Contact: Tomer Mark, M.D. (646) 962-2071 tom9009@med.cornell.edu

Locations
United States, New York
Weill Cornell Medicial College Recruiting
New York, New York, United States, 10021
Contact: Linda Tegnestam, R.N.    212-746-1480    lit2011@med.cornell.edu   
Principal Investigator: Tomer Mark, M.D.         
Sub-Investigator: Ruben Niesvizky, M.D.         
Sub-Investigator: Roger Pearse, M.D.         
Sub-Investigator: Tsiporah Shore, M.D.         
Sponsors and Collaborators
Weill Medical College of Cornell University
Onyx Therapeutics, Inc.
Investigators
Principal Investigator: Tomer Mark, M.D. Weill Cornell Medicial College
  More Information

No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01559935     History of Changes
Other Study ID Numbers: 1108011903
Study First Received: February 16, 2012
Last Updated: June 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
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
Clarithromycin
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

ClinicalTrials.gov processed this record on October 20, 2014