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

NCT01464034 | Terminated Phase 1

• 3 other identifiers: AMyC 10-MM-01IST-CAR-521PO-MM-PI-0034
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 9

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• Overall Response in Phase I

  Every 28 days while on treatment (estimated at 2- 12 months per patient)

• Time to Progression

  Every 28 days while on treatment (estimated at 2-12 months per patient)

• Progression Free Survival

  throughout follow up (every 2-3 months for 2 years)

• Time to next therapy

  throughout follow up (every 2-3 months for 2 years)

Study Arms (1)

Carfilzomib, Pomalidomide, Dexamethasone

EXPERIMENTAL

All eligible subjects will receive the study intervention of Carfilzomib, Pomalidomide, and Dexamethasone.

Drug: Carfilzomib; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

IV over 30 minutes on Days 1,2,8,9,15, and 16 every 28 days

Also known as: PR-171

Carfilzomib, Pomalidomide, Dexamethasone

Pomalidomide DRUG

PO daily on Days 1-21, every 28 Days

Also known as: CC-4047

Carfilzomib, Pomalidomide, Dexamethasone

Dexamethasone DRUG

40 mg weekly PO or IV on Days 1, 8, 15, and 22, every 28 days.

Also known as: Decadron

Carfilzomib, Pomalidomide, Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Criterium, Inc.: lead
• Amgen: collaborator
• Celgene Corporation: collaborator

Study Sites (9)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

The John Theurer Cancer Center @ Hackensack UMC

Hackensack, New Jersey, 07601, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19105, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 26384354 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; pomalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Jatin Shah, MD

  AMyC

  PRINCIPAL INVESTIGATOR

• Brian GM Durie, MD

  AMyC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2011
• First Posted: November 3, 2011
• Study Start: November 1, 2011
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: August 1, 2022

Record last verified: 2022-07

Locations

US (9)