A Safety Study of Carfilzomib, Cyclophosphamide & Dexamethasone Prior to ASCT in Patients With Newly Diagnosed Myeloma (11-MM-01)

October 16, 2017 updated by: Criterium, Inc.

A Multi-Center Phase Ib, Open-Label, Dose-Finding Pilot Study to Evaluate the Combination of Carfilzomib and Cyclophosphamide With Dexamethasone Prior to ASCT in Patients With Transplant Eligible Newly Diagnosed Myeloma

This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex) prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant eligible multiple myeloma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 cyclophosphamide with dexamethasone (Car-Cy-Dex) prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant eligible multiple myeloma. The study will also explore the efficacy of Car-Cy-Dex including overall response after induction therapy, overall response at 3 and 6 months post ASCT, and time to progression, progression free survival, and time to next therapy if it occurs within 6 months post ASCT.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Samuel Oschin Comprehensive Cancer Center at Cedars-Sinai Medical Center
      • Palm Springs, California, United States, 92262
        • Comprehensive Cancer Center at Desert Regional Medical Center
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusettes Memorial
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Cytopathologically or histologically confirmed diagnosis of MM
  • Measurable disease, as indicated by one or more of the following:
  • Serum M-protein ≥ 1.0 g/dL
  • Urine Bence Jones protein ≥ 200 mg/24 hr
  • Elevated Free Light Chain as per the International Myeloma Working Group (IMWG) criteria
  • Males and females ≥ 18 years of age
  • Life expectancy of more than 5 months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.5 times ULN
  • Serum Creatinine Clearance(CrCl) ≥ 30 mL/min, either measured or calculated using a standard formula (e.g. Cockcroft and Gault)
  • Additional Laboratory Requirements
  • Absolute neutrophil count (ANC) ≥1.0 x 109/L
  • Hemoglobin ≥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
  • Patients may receive RBC or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Patients must agree to practice contraception
  • Male patients must agree not to donate semen or sperm.

Exclusion Criteria:

  • Patients with non-secretory or hyposecretory MM
  • Prior treatment for MM (prior radiation therapy or dexamethasone up to 160 mg for spinal cord compression is allowed. Other limited field radiation involving ≤ 1/3 of the pelvic area is also allowed)
  • Plasma cell leukemia
  • Pregnant or lactating females
  • Major surgery within 21 days prior to first dose
  • Congestive heart failure (CHF) (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose
  • Patients receiving active treatment or intervention for any other malignancy or patients 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 study treatment
  • Contraindication to any of the required concomitant drugs, including antiviral (e.g. Valacyclovir) and proton-pump inhibitor (e.g. lansoprazole). Corticosteroid therapy in a dose equivalent to dexamethasone ≥ 1.5 mg/day or prednisone ≥ 10 mg/day. (Steroid use is allowed if necessary to treat spinal cord compression and/or hypocalcaemia.)
  • Patients in whom the required program of oral and IV fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment
  • Patients with primary systemic amyloidosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Carfilzomib, Cyclophosphamide, Dexamethasone
All eligible subjects will receive Carfilzomib, Cyclophosphamide, and Dexamethasone.
Drug: Carfilzomib
IV over 30 minutes on Days 1,2,8,9,15, and 16 every 28 days
Other Names:
  • Kyprolis
  • PR-171
Drug: Dexamethasone
40 mg weekly PO or IV on Days 1, 8, 15, and 22, every 28 days.
Other Names:
  • Decadron
Drug: Cyclophosphamide
PO on days 1, 8, and 15 every 28 days
Other Names:
  • Cytoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events as a measure of safety and tolerability
Time Frame: Throughout treatment, estimated to be 4-6 months per patients
Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.
Throughout treatment, estimated to be 4-6 months per patients

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response after induction therapy
Time Frame: Every 28 days during induction therapy, estimated to be 4-6 months
Overall response (PR, VGPR, CR, sCR)
Every 28 days during induction therapy, estimated to be 4-6 months
Overall Response post ASCT
Time Frame: 3 and 6 months post ASCT
Overall Response (PR, VGPR, CR, sCR) at 3 and 6 months post ASCT.
3 and 6 months post ASCT
Time to Progression
Time Frame: Througout treatment and 3 and 6 months post ASCT
Time to progression will be noted if it occurs within 6 months post ASCT.
Througout treatment and 3 and 6 months post ASCT
Progression Free Survival
Time Frame: up to 6 months post ASCT
up to 6 months post ASCT
Time to Next Therapy
Time Frame: up to 6 months post ASCT
Time to Next Therapy if occurs within 6 months post ASCT
up to 6 months post ASCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Criterium, Inc.

Collaborators

Amgen

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

August 7, 2012

First Submitted That Met QC Criteria

August 7, 2012

First Posted (Estimate)

August 9, 2012

Study Record Updates

Last Update Posted (Actual)

October 18, 2017

Last Update Submitted That Met QC Criteria

October 16, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMyC 11-MM-01
  • CAR-IST-520 (Other Identifier: Onyx Pharmaceuticals)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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