Clinical trial NCT01464034: A Safety and Efficacy Study of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Criterium, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Amgen
name: Celgene Corporation
First posted: 2011-11-03
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Adverse Events as a Measure of Safety and Tolerability
timeFrame: Throughout treatment, estimated at 2-12 months per patient
measure: Overall Response in Phase II
timeFrame: Every 28 days while on treatment (estimated at 2- 12 months per patient)
Secondary outcomes:
measure: Overall Response in Phase I
timeFrame: Every 28 days while on treatment (estimated at 2- 12 months per patient)
measure: Time to Progression
timeFrame: Every 28 days while on treatment (estimated at 2-12 months per patient)
measure: Progression Free Survival
timeFrame: throughout follow up (every 2-3 months for 2 years)
measure: Time to next therapy
timeFrame: throughout follow up (every 2-3 months for 2 years)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Hackensack
country: United States
facility: The John Theurer Cancer Center @ Hackensack UMC
state: New Jersey
city: New York
country: United States
facility: Columbia University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: AMyC
name: Jatin Shah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AMyC
name: Brian GM Durie, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.