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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Academic Myeloma Consortium
Sponsor:
Collaborator:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Academic Myeloma Consortium
ClinicalTrials.gov Identifier:
NCT01660750
First received: August 7, 2012
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Carfilzomib
Drug: Cyclophosphamide
Drug: Dexamethasone
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Academic Myeloma Consortium:

Primary Outcome Measures:
  • Adverse Events as a measure of safety and tolerability [ Time Frame: Throughout treatment, estimated to be 4-6 months per patients ] [ Designated as safety issue: Yes ]
    Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.


Secondary Outcome Measures:
  • Overall Response after induction therapy [ Time Frame: Every 28 days during induction therapy, estimated to be 4-6 months ] [ Designated as safety issue: No ]
    Overall response (PR, VGPR, CR, sCR)

  • Overall Response post ASCT [ Time Frame: 3 and 6 months post ASCT ] [ Designated as safety issue: No ]
    Overall Response (PR, VGPR, CR, sCR) at 3 and 6 months post ASCT.

  • Time to Progression [ Time Frame: Througout treatment and 3 and 6 months post ASCT ] [ Designated as safety issue: No ]
    Time to progression will be noted if it occurs within 6 months post ASCT.

  • Progression Free Survival [ Time Frame: up to 6 months post ASCT ] [ Designated as safety issue: No ]
  • Time to Next Therapy [ Time Frame: up to 6 months post ASCT ] [ Designated as safety issue: No ]
    Time to Next Therapy if occurs within 6 months post ASCT


Estimated Enrollment: 38
Study Start Date: January 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carfilzomib, Cyclophosphamide, Dexamethasone
All eligible subjects will receive the study intervention of Carfilzomib, Cyclophosphamide, and Dexamethasone.
Drug: Carfilzomib
IV over 30 minutes on Days 1,2,8,9,15, and 16 every 28 days
Other Names:
  • PR-171
  • Kyprolis
Drug: Cyclophosphamide
PO on days 1, 8, and 15 every 28 days
Other Name: Cytoxan
Drug: Dexamethasone
40 mg weekly PO or IV on Days 1, 8, 15, and 22, every 28 days.
Other Name: Decadron

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01660750

Locations
United States, California
Samuel Oschin Comprehensive Cancer Center at Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Dominique Durant    310-248-8542    dominique.durant@cshs.org   
Contact: Premere Sessions       premere.knowles@cshs.org   
Principal Investigator: Robert Vescio, MD         
Comprehensive Cancer Center at Desert Regional Medical Center Recruiting
Palm Springs, California, United States, 92262
Contact: Claudia Fortiche    760-416-4736    claudia.fortiche@tenethealth.com   
Principal Investigator: Elber Camacho, MD         
United States, Massachusetts
University of Massachusettes Memorial Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Donna doBuono    508-856-1959    donna.dibuono2@umassmemorial.org   
Contact: Kathryn Clarke       Kathryn.Clarke@umassmemorial.org   
Principal Investigator: Rajneesh Nath, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Kimberly Oates    919-668-6524    kimberly.bartlett@dm.duke.edu   
Principal Investigator: Cristina Gasparetto, MD         
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Cari Morin    206-667-6238    cmorin@fhcrc.org   
Principal Investigator: William Bensinger, MD         
Sponsors and Collaborators
Academic Myeloma Consortium
Onyx Pharmaceuticals
Investigators
Principal Investigator: Jatin Shah, MD Academic Myeloma Consortium
Principal Investigator: Brian GM Durie, MD Academic Myeloma Consortium
  More Information

No publications provided

Responsible Party: Academic Myeloma Consortium
ClinicalTrials.gov Identifier: NCT01660750     History of Changes
Other Study ID Numbers: AMyC 11-MM-01, CAR-IST-520
Study First Received: August 7, 2012
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Academic Myeloma Consortium:
newly diagnosed multiple myeloma
transplant eligible multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents

ClinicalTrials.gov processed this record on October 29, 2014