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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01464034
• Other study ID #: AMyC 10-MM-01
• Secondary ID: IST-CAR-521PO-MM
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 2011
• Est. completion date: July 2020

Study information

• Verified date: July 2022
• Source: Criterium, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 136
• Est. completion date: July 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib
IV over 30 minutes on Days 1,2,8,9,15, and 16 every 28 days
• Pomalidomide
PO daily on Days 1-21, every 28 Days
• Dexamethasone
40 mg weekly PO or IV on Days 1, 8, 15, and 22, every 28 days.

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Duke University Medical Center	Durham	North Carolina
United States	The John Theurer Cancer Center @ Hackensack UMC	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Columbia University	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Criterium, Inc.	Amgen, Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events as a Measure of Safety and Tolerability	Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.	Throughout treatment, estimated at 2-12 months per patient
Primary	Overall Response in Phase II	Overall Response (SD, MR, PR, VGPR, CR, sCR)	Every 28 days while on treatment (estimated at 2- 12 months per patient)
Secondary	Overall Response in Phase I	Overall response (SD, MR, PR, VGPR, CR, sCR)	Every 28 days while on treatment (estimated at 2- 12 months per patient)
Secondary	Time to Progression		Every 28 days while on treatment (estimated at 2-12 months per patient)
Secondary	Progression Free Survival		throughout follow up (every 2-3 months for 2 years)
Secondary	Time to next therapy		throughout follow up (every 2-3 months for 2 years)