A Safety and Efficacy Study of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Conditions
Multiple Myeloma
Conditions: official terms
Multiple Myeloma - Neoplasms, Plasma Cell
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Carfilzomib Type: Drug
Name: Pomalidomide Type: Drug
Name: Dexamethasone Type: Drug
Overall Status
Recruiting
Summary
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.
Detailed Description
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Cytopathologically or histologically confirmed dx of multiple myeloma

- Relapsed or refractory to the most recently received therapy.

- All pts must have received prior lenalidomide therapy and been determined to be refractory, relapsed, or intolerant.

- 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

- Pts must be ≥ 18 years of age

- Life expectancy of more than 3 months

- ECOG PS 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

- CrCl ≥ 50 mL/min

- Additional Laboratory Requirements ANC ≥1.0 x 109/L Hgb ≥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

- Pts may receive 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

- FCBP must agree to ongoing pregnancy testing

- FCBP must have a negative serum or urine pregnancy test and agree to birth control.

- Male pts 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. 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 pts cannot donate semen or sperm while taking pomalidomide and for 28 days after completing the study.

- All pts must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

- Pts 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:

- Pts 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. Pts 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)

- Current diagnosis of plasma cell leukemia

- Waldenström's macroglobulinemia

- Major surgery within 21 days prior to first dose

- Pregnant or lactating females

- Congestive heart failure (NYHA 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

- Pts receiving active treatment or intervention for any other malignancy or pts 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

- Pts in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment

- Pts with primary systemic amyloidosis

- Pts who have received prior treatment with carfilzomib (Phase II only)

- Pts who have received prior treatment with pomalidomide (Phase II only)

- Pts who have received prior treatment with both carfilzomib & pomalidomide (Phase I only)
Locations
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Status: Recruiting
Contact: Alaina Mitchell - 404-778-5747 - alaina.r.mitchell@emory.edu
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States
Status: Recruiting
Contact: Mary Cangany - 317-274-2178 - mcangany@iupui.edu
The John Theurer Cancer Center @ Hackensack UMC
Hackensack, New Jersey, United States
Status: Recruiting
Contact: Laura Raucci - 551-996-5683 - lraucci@hackensackumc.org
Columbia University
New York, New York, United States
Status: Recruiting
Contact: Tasha Smith - 212-305-2460 - ts2257@columbia.edu
Duke University Medical Center
Durham, North Carolina, United States
Status: Recruiting
Contact: Kimberly Oates, RN - 919-668-6524 - kimberly.bartlett@duke.edu
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Status: Terminated
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Status: Terminated
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States
Status: Withdrawn
MD Anderson Cancer Center
Houston, Texas, United States
Status: Recruiting
Contact: CR Study Reg Team - 713-745-6130 - jjshah@mdanderson.org
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Status: Recruiting
Contact: Chinh Nguyen - 206-667-5936 - chnguyen@fhcrc.org
Start Date
November 2011
Completion Date
June 2020
Sponsors
Academic Myeloma Consortium
Source
Academic Myeloma Consortium
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page