Carfilzomib in Treating Patients With Multiple Myeloma in First Relapse or Refractory to First-Line Therapy

NCT02020941 | Terminated Phase 2 Results DMC

• 3 other identifiers: IUCRO-0414NCI-2013-01771P30CA082709
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well carfilzomib works in treating patients with multiple myeloma in first relapse or refractory to first-line therapy. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) After 8 Courses of Treatment

  : Evaluate the overall response rate of patients receiving therapy. Patients are considered as having a response if their overall response is Partial Response or better. The percentage of patients achieving this and the exact 95% confidence interval will be calculated. Responses will be defined using the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).

  At 32 weeks

Secondary Outcomes (5)

• Overall Response Rate (ORR) After 4 Courses of Treatment

  At 16 weeks

• Progression-free Survival (PFS)

  Time from first dose to first observed disease progression or death, assessed up to 2 years

• Time to Progression (TTP)

  Time from first dose to disease progression, assessed up to 2 years

• Duration of Response (DOR)

  Time from first evidence of PR or better to disease progression or death, assessed up to 2 years

• Treatment Related Adverse Events Grade 3 or Higher

  Up to 30 days after completion of study treatment, up to 2 years

Study Arms (1)

Treatment (carfilzomib, dexamethasone)

EXPERIMENTAL

TREATMENT PHASE (COURSES 1-8): Patients receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving less than PR also receive dexamethasone PO or IV weekly in courses 4-8. MAINTENANCE PHASE (COURSES 9-14): Patients receive carfilzomib IV over 30 minutes on days 1, 2, 15, and 16. Patients who received dexamethasone in the Treatment Phase continue to receive dexamethasone PO or IV weekly. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: carfilzomib; Drug: dexamethasone; Other: laboratory biomarker analysis

Interventions

carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Treatment (carfilzomib, dexamethasone)

dexamethasone DRUG

Given IV or PO

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Treatment (carfilzomib, dexamethasone)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (carfilzomib, dexamethasone)

Eligibility Criteria

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

You may qualify if:

• Multiple myeloma (MM) in first relapse or refractory to first line therapy; the previous line of therapy should include either an immunomodulatory agent or a proteasome inhibitor
• Refractory disease is defined as =\< 25% response or progression during therapy or within 60 days after completion
• The number of prior lines of anti-myeloma therapy will be determined as follows:
• Induction chemotherapy for peripheral-blood stem cell harvest followed by planned mobilization and subsequent high-dose chemotherapy with autologous stem cell transplant (ASCT) is considered one therapy regardless of the induction regimen
• Planned maintenance therapy after stem cell transplantation or other induction therapy is not considered a separate line of therapy, as long as there is no evidence of progression in the time between the induction or transplantation and the initiation of maintenance therapy
• Two ASCTs within 6 months of each other is considered as one line unless different agents were used in the high-dose therapy-conditioning regimens
• If the same regimen is repeated after a 6-month interval, they are considered to be two separate therapeutic lines
• If cyclophosphamide is used for reasons other than planned stem cell mobilization, its use is considered to be a separate line of therapy
• Dose modification of steroid and altering choices of steroid (i.e. from dexamethasone to prednisone) due to side effects, is not considered a line of therapy, as long as there is no evidence of progression
• If a regimen was stopped for more than 2 months, its re-initiation is counted as another line of therapy
• Presence of existing lytic bone lesions either by skeletal X-ray, computed tomography (CT) scan or magnetic resonance imaging (MRI) scan
• Measurable MM disease, defined as one of the following:
• A monoclonal immunoglobulin (Ig) concentration on serum electrophoresis of \>= 0.5 g/dL for an IgG myeloma, \>= 0.1 g/dL for an IgD myeloma or \>= 0.5 g/dL for an IgA myeloma
• Measurable urinary light chain secretion by quantitative analysis of \>= 200 mg/24 hours
• Involved serum free light chain (FLC) level \>= 10 mg/dL, provided the serum FLC ratio is abnormal

You may not qualify if:

• No primary amyloidosis
• No plasma cell leukemia (\> 2.0 × 10\^9/L circulating plasma cells by standard differential)
• No treatment with an investigational product or device within 21 days of cycle 1 day 1
• No history of allergic reaction/hypersensitivity to any of the study medications, their analogues or excipients in the various formulations
• No treatment with cytotoxic therapy or monoclonal antibodies within 21 days prior to cycle 1 day 1
• No treatment with a steroid intended to treat myeloma within 14 days prior to cycle 1 day 1
• No autologous or allogeneic stem cell transplant within 3 months prior to cycle 1 day 1
• No radiotherapy within 21 days prior to cycle 1 day 1; however, if the radiation portal covered =\< 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy
• No major surgery within 14 days and minor surgery within 7 days prior to cycle 1 day 1
• No pregnant or lactating females
• No acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to cycle 1 day 1
• No known human immunodeficiency virus (HIV) infection
• No active hepatitis B or C infection
• No unstable angina or myocardial infarction within 4 months prior to cycle 1 day 1, New York Heart Association (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
• No uncontrolled hypertension or uncontrolled diabetes (as determined by the treating physician) within 14 days prior to cycle 1 day 1

Sponsors & Collaborators

• Attaya Suvannasankha: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; 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

Results Point of Contact

• Title: Dr. Attaya Suvannasankha
• Organization: IndianaU

asuvanna@iu.edu

317-944-0920

Study Officials

• Attaya Suvannasankha

  Indiana University School of Medicine

  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: Principal Investigator

Study Record Dates

• First Submitted: December 19, 2013
• First Posted: December 25, 2013
• Study Start: September 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: April 1, 2016
• Last Updated: November 2, 2016
• Results First Posted: November 2, 2016

Record last verified: 2016-07

Locations

US (1)