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

• Sponsor: Criterium, Inc.
• Collaborators: Amgen; Celgene Corporation
• Information provided by (Responsible Party): Criterium, Inc.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Carfilzomib; Drug: Pomalidomide; Drug: Dexamethasone	Phase 1; Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	117 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	November 2011
Estimated Primary Completion Date :	December 2017
Estimated Study Completion Date :	June 2018

Arms and Interventions

Arm	Intervention/treatment
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.; Other Name: Decadron

Outcome Measures

Primary Outcome Measures :

1. Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Throughout treatment, estimated at 2-12 months per patient ]
   Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.
2. Overall Response in Phase II [ Time Frame: Every 28 days while on treatment (estimated at 2- 12 months per patient) ]
   Overall Response (SD, MR, PR, VGPR, CR, sCR)

Secondary Outcome Measures :

1. Overall Response in Phase I [ Time Frame: Every 28 days while on treatment (estimated at 2- 12 months per patient) ]
   Overall response (SD, MR, PR, VGPR, CR, sCR)
2. Time to Progression [ Time Frame: Every 28 days while on treatment (estimated at 2-12 months per patient) ]
3. Progression Free Survival [ Time Frame: throughout follow up (every 2-3 months for 2 years) ]
4. Time to next therapy [ Time Frame: throughout follow up (every 2-3 months for 2 years) ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Locations

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United States, Georgia
Winship Cancer Institute of Emory University	Recruiting
Atlanta, Georgia, United States, 30322
Contact: Yan Li 404-778-4713 yli9@emory.edu
Principal Investigator: Jonathan Kaufman, MD
United States, Indiana
Indiana University Simon Cancer Center	Terminated
Indianapolis, Indiana, United States, 46202
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	Terminated
New York, New York, United States, 10032
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	Terminated
Philadelphia, Pennsylvania, United States, 19105
Fox Chase Cancer Center	Terminated
Philadelphia, Pennsylvania, United States, 19111
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: Hermon Berhane hberhane@fredhutch.org
Principal Investigator: Edward Libby, MD

Sponsors and Collaborators

Criterium, Inc.

Amgen

Celgene Corporation

Investigators

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Principal Investigator:	Jatin Shah, MD	AMyC
Principal Investigator:	Brian GM Durie, MD	AMyC

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C, Kaufman JL, Lentzsch S, Vogl DT, Gomes CL, Pascucci N, Smith DD, Orlowski RZ, Durie BG. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015 Nov 12;126(20):2284-90. doi: 10.1182/blood-2015-05-643320. Epub 2015 Sep 17.

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Responsible Party:	Criterium, Inc.
ClinicalTrials.gov Identifier:	NCT01464034 History of Changes
Other Study ID Numbers:	AMyC 10-MM-01; IST-CAR-521 ( Other Identifier: Onyx Pharmaceuticals ); PO-MM-PI-0034 ( Other Identifier: Celgene Corporation )
First Posted:	November 3, 2011
Last Update Posted:	October 18, 2017
Last Verified:	October 2017

Additional relevant MeSH terms:

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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	Dexamethasone acetate; Pomalidomide; Thalidomide; BB 1101; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents