A Safety and Efficacy Study of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Academic Myeloma Consortium
Sponsor:
Collaborators:
Criterium Inc.
Onyx Pharmaceuticals
Celgene Corporation
Information provided by (Responsible Party):
Academic Myeloma Consortium
ClinicalTrials.gov Identifier:
NCT01464034
First received: October 19, 2011
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and pomalidomide with dexamethasone (CPD) in patients with relapsed or refractory multiple myeloma followed by a phase II expansion at the MTD to evaluate efficacy. The study will explore the efficacy of CPD including overall response, time to progression, progression free survival, and time to next therapy.


Condition Intervention Phase
Multiple Myeloma
Drug: Carfilzomib
Drug: Pomalidomide
Drug: 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: Treatment
Official Title: A Multi-Center Phase I/II, Open-Label, Dose-Finding Pilot Study of the Combination of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Academic Myeloma Consortium:

Primary Outcome Measures:
  • Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Throughout treatment, estimated at 2-12 months per patient ] [ Designated as safety issue: Yes ]
    Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.

  • Overall Response in Phase II [ Time Frame: Every 28 days while on treatment (estimated at 2- 12 months per patient) ] [ Designated as safety issue: No ]
    Overall Response (SD, MR, PR, VGPR, CR, sCR)


Secondary Outcome Measures:
  • Overall Response in Phase I [ Time Frame: Every 28 days while on treatment (estimated at 2- 12 months per patient) ] [ Designated as safety issue: No ]
    Overall response (SD, MR, PR, VGPR, CR, sCR)

  • Time to Progression [ Time Frame: Every 28 days while on treatment (estimated at 2-12 months per patient) ] [ Designated as safety issue: No ]
  • Progression Free Survival [ Time Frame: throughout follow up (every 2-3 months for 2 years) ] [ Designated as safety issue: No ]
  • Time to next therapy [ Time Frame: throughout follow up (every 2-3 months for 2 years) ] [ Designated as safety issue: No ]

Estimated Enrollment: 117
Study Start Date: November 2011
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carfilzomib, Pomalidomide, Dexamethasone
All eligible subjects will receive the study intervention of Carfilzomib, Pomalidomide, and Dexamethasone.
Drug: Carfilzomib
IV over 30 minutes on Days 1,2,8,9,15, and 16 every 28 days
Other Name: PR-171
Drug: Pomalidomide
PO daily on Days 1-21, every 28 Days
Other Name: CC-4047
Drug: Dexamethasone
40 mg weekly PO or IV on Days 1, 8, 15, and 22, every 28 days.

  Eligibility

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

Inclusion Criteria:

  • Cytopathologically or histologically confirmed diagnosis of multiple myeloma
  • Relapsed or refractory to the most recently received therapy. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion.
  • All patients must have received prior lenalidomide therapy and been determined to be refractory. Refractory will be defined as ≤ 25% response or progression during therapy or within 60 days after completion of a regimen containing full or maximally tolerated dose of lenalidomide administered for at least two completed cycles of therapy.
  • Measurable disease, as indicated by one or more of the following:

Serum M-protein ≥ 0.5 g/dL Urine Bence Jones protein ≥ 200 mg/24 hr Elevated Free Light Chain as per IMWG criteria, and abnormal ratio

  • Males and females ≥ 18 years of age
  • Life expectancy of more than 3 months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN
  • Uric acid must be within laboratory normal range
  • Creatinine Clearance ≥ 50 mL/min
  • Additional Laboratory Requirements Absolute neutrophil count (ANC) ≥1.0 x 109/L Hemoglobin ≥8 g/dL(transfusion permitted) Platelet count ≥50.0 x 109/L
  • Screening ANC should be independent of granulocyte-and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks
  • Patients may receive red blood cell (RBC) or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
  • Screening platelet count should be independent of platelet transfusions for at least 2 weeks.
  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Females of childbearing potential (FCBP)must agree to ongoing pregnancy testing
  • FCBP must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting pomalidomide 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, beginning 2 weeks prior to initiating treatment with pomalidomide, during treatment, during treatment delay, and continuing for 4 weeks following discontinuation of pomalidomide therapy. If a hormonal method or IUD is not medically possible for the patient, the patient may use another highly effective method or two barrier methods at the same time.
  • Male patients must agree to never have unprotected sexual contact with a female who can become pregnant and must agree to either completely abstain from sexual contact with females who are pregnant or are able to become pregnant, or he must use a latex condom every time he engages in sexual contact with females who are pregnant or may become pregnant while he is taking pomalidomide and for 4 weeks after he stops taking the drug, even if he has had a successful vasectomy. The patient must agree to inform his physician if he has had unprotected sexual contact with a female who can become pregnant or if he thinks for any reason that his sexual partner may be pregnant.
  • Male patients cannot donate semen or sperm while taking pomalidomide and for 28 days after completing the study.
  • All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
  • Patients must agree to take enteric-coated aspirin 81 mg orally daily, or if history of prior thrombotic disease, must be fully anticoagulated with warfarin (INR 2-3) or be treated with full-dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism (PE)at the investigator's discretion

Exclusion Criteria:

  • Patients with known sensitivity to any immunomodulatory drugs (IMiDs)
  • • Use of any other experimental drug or therapy within 21 days prior to first dose
  • Exposure to any prior chemotherapy, steroid use, or other myeloma treatment within 14 days prior to first dose. Patients currently on long term steroids do not require any washout period. in addition, steroid use for spinal cord compression is permitted and does not require a washout period.
  • Radiation therapy within 14 days prior to first dose
  • Known allergies to carfilzomib or Captisol
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Plasma cell leukemia
  • Waldenström's macroglobulinemia
  • Major surgery within 21 days prior to first dose
  • Pregnant or lactating females
  • Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months prior to first dose.
  • Uncontrolled hypertension
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose
  • Patients receiving active treatment or intervention for any other malignancy or patients who, at the Investigator's discretion, may require active treatment or intervention for any other malignancy within 8 months of starting study treatment.
  • Serious psychiatric or medical conditions that could interfere with treatment
  • Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days before enrollment
  • Contraindication to any of the required concomitant drugs, including proton-pump inhibitor (e.g. lansoprazole), enteric-coated aspirin or if a history of prior thrombotic disease, warfarin or low molecular weight heparin
  • Patients in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment
  • Patients with primary systemic amyloidosis
  • Patients who have received prior treatment with carfilzomib (Phase II only)
  • Patients who have received prior treatment with pomalidomide (Phase II only)
  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: NCT01464034

Locations
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Alaina Mitchell    404-778-5747    alaina.r.mitchell@emory.edu   
Principal Investigator: Jonathan Kaufman, MD         
United States, Indiana
Indiana University Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Mary Cangany    317-274-2178    mcangany@iupui.edu   
Principal Investigator: Rafat Abonour, MD         
United States, New Jersey
The John Theurer Cancer Center @ Hackensack UMC Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Laura Raucci    551-996-5683    lraucci@hackensackumc.org   
Principal Investigator: David Siegel, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Tasha Smith    212-305-2460    ts2257@columbia.edu   
Principal Investigator: Suzanne Lentzsch, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Kimberly Oates, RN    919-668-6524    kimberly.bartlett@duke.edu   
Principal Investigator: Cristina Gasparetto, MD         
United States, Pennsylvania
University of Pennsylvania Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19105
Contact: Edward Stadtmauer, MD    215-662-7910    edward.stadtmauer@uphs.upenn.edu   
Principal Investigator: Edward Stadtmauer, MD         
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Linda Thibodeau    215-728-2207    linda.thibodeau@fccc.edu   
Principal Investigator: Adam Cohen, MD         
University of Pittsburgh Cancer Institute Withdrawn
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: CR Study Reg Team    713-745-6130    jjshah@mdanderson.org   
Principal Investigator: Jatin Shah, MD         
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Chinh Nguyen    206-667-5936    chnguyen@fhcrc.org   
Principal Investigator: William Bensinger, MD         
Sponsors and Collaborators
Academic Myeloma Consortium
Criterium Inc.
Onyx Pharmaceuticals
Celgene Corporation
Investigators
Principal Investigator: Jatin Shah, MD Academic Myeloma Consortium
Principal Investigator: Brian GM Durie, MD Academic Myeloma Consortium
  More Information

No publications provided

Responsible Party: Academic Myeloma Consortium
ClinicalTrials.gov Identifier: NCT01464034     History of Changes
Other Study ID Numbers: AMyC 10-MM-01, IST-CAR-521, PO-MM-PI-0034
Study First Received: October 19, 2011
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on July 10, 2014