Study of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib

NCT01775553 | Completed Phase 2 Results DMC

• 2 other identifiers: GCO 12-1506CAR IST 534
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and activity of the investigational drug known as carfilzomib in the treatment of multiple myeloma (MM) when it is given at doses above the usual dose after the standard dosing has become ineffective. The other purpose of this study is to understand what causes the multiple myeloma to become resistant to carfilzomib and whether this can be overcome in the laboratory.

Conditions

Relapse Multiple Myeloma; Refractory Multiple Myeloma

Keywords

Relapsed Multiple Myeloma; Refractory Multiple Myeloma; High-Dose Carfilzomib; Standard Dose Carfilzomib; Carfilzomib

Outcome Measures

Primary Outcomes (1)

• Safety and Efficacy of High Dose Carfilzomib

  The safety and efficacy of high dose carfilzomib who developed disease progression on the standard dosing and schedule of carfilzomib as measured by number of participants with adverse events

  up to 4 years

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  up to 4 years

• Overall Response Rate (ORR)

  up to 4 years

• Duration of Response to High Dose Carfilzomib

  up to 4 years

• Markers of ER Stress

  up to 4 years

Study Arms (1)

Carfilzomib

EXPERIMENTAL

All patients will receive Carfilzomib

Drug: Carfilzomib

Interventions

Carfilzomib DRUG

During Cycle 1, patients will receive either 20 mg/m2 on days 1,2 (if the subject has not received carfilzomib as part another clinical trial within the last 4 weeks) or 56 mg/m2 (if the subject is enrolling in the present study after progression of disease on carfilzomib within the last month - for example subjects enrolled in CMAP compassionate use carfilzomib). Thereafter, all subjects will receive 56 mg/m2 for the remaining doses given Cycle 1 Day 8 onwards. Each cycle is 28 days.

Also known as: High Dose Carfilzomib

Carfilzomib

Eligibility Criteria

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

You may qualify if:

• Disease-related:
• Multiple myeloma
• Subjects must have measurable disease, defined as one or both of the following:
• Serum M-protein ≥ 1.0 g/dL
• Urine M-protein ≥ 200 mg/24 hours
• Free light chains: Only in patients without measureable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels must be at least 10 mg/dl.
• Refractory to the most recently received therapy. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy.
• Subjects must have progressed on standard dose 20/27 mg/m2 and schedule of carfilzomib without having had any carfilzomib related grade 3 or 4 toxicities.
• Subjects must have received ≥ 2 prior regimens for relapsed disease. Induction therapy and stem cell transplant will be considered as one regimen
• Subjects must have received prior treatment with bortezomib, and either thalidomide or lenalidomide
• Subjects must have received an alkylating agent unless contraindicated. Subjects may have received these agents alone or in combination with other myeloma treatments.
• Demographic:
• Age ≥ 18 years
• Life expectancy ≥ 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

You may not qualify if:

• Disease-related
• Glucocorticoid therapy (prednisone \> 10 mg/day or equivalent) within the last three weeks
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the three weeks prior to first dose (unless enrolling on this study after progression CMAP compassionate use carfilzomib protocol, in which case subject may proceed with current study treatment on next expected date of treatment)
• Radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose
• Participation in an investigational therapeutic study within three weeks or within five drug half-lives (t1/2) prior to first dose, whichever time is greater (unless enrolling after progression on CMAP compassionate use carfilzomib protocol)
• Concurrent Conditions
• Pregnant or lactating females
• Major surgery within 21 days prior to randomization
• Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization
• Known human immunodeficiency virus infection
• Known active hepatitis B or C infection
• Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomization
• Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas

Sponsors & Collaborators

• Ajai Chari: lead
• Amgen: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib

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

Results Point of Contact

• Title: Dr. Ajai Chari
• Organization: Icahn School of Medicine at Mount Sinai

ajai.chari@mountsinai.org

212-241-7873

Study Officials

• Ajai Chari, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 25, 2012
• First Posted: January 25, 2013
• Study Start: September 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: June 21, 2017
• Results First Posted: June 21, 2017

Record last verified: 2017-05

Locations

US (1)