A Safety Study of Carfilzomib, Cyclophosphamide & Dexamethasone Prior to ASCT in Patients With Newly Diagnosed Myeloma

NCT01660750 | Completed Phase 1

• 2 other identifiers: AMyC 11-MM-01CAR-IST-520
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

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 cyclophosphamide with dexamethasone (Car-Cy-Dex) prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant eligible multiple myeloma.

Conditions

Multiple Myeloma

Keywords

newly diagnosed multiple myeloma; transplant eligible multiple myeloma

Outcome Measures

Primary Outcomes (1)

• 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 to be 4-6 months per patients

Secondary Outcomes (5)

• Overall Response after induction therapy

  Every 28 days during induction therapy, estimated to be 4-6 months

• Overall Response post ASCT

  3 and 6 months post ASCT

• Time to Progression

  Througout treatment and 3 and 6 months post ASCT

• Progression Free Survival

  up to 6 months post ASCT

• Time to Next Therapy

  up to 6 months post ASCT

Study Arms (1)

Carfilzomib, Cyclophosphamide, Dexamethasone

EXPERIMENTAL

All eligible subjects will receive Carfilzomib, Cyclophosphamide, and Dexamethasone.

Drug: Carfilzomib; Drug: Cyclophosphamide; 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, Kyprolis

Carfilzomib, Cyclophosphamide, Dexamethasone

Cyclophosphamide DRUG

PO on days 1, 8, and 15 every 28 days

Also known as: Cytoxan

Carfilzomib, Cyclophosphamide, Dexamethasone

Dexamethasone DRUG

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

Also known as: Decadron

Carfilzomib, Cyclophosphamide, 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 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Criterium, Inc.: lead
• Amgen: collaborator

Study Sites (5)

Samuel Oschin Comprehensive Cancer Center at Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Comprehensive Cancer Center at Desert Regional Medical Center

Palm Springs, California, 92262, United States

Location

University of Massachusettes Memorial

Worcester, Massachusetts, 01655, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Cyclophosphamide; 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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; 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: August 7, 2012
• First Posted: August 9, 2012
• Study Start: January 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: December 1, 2015
• Last Updated: October 18, 2017

Record last verified: 2017-10

Locations

US (5)