Weekly 70 mg/m2 Carfilzomib for Multiple Myeloma Patients Refractory to 27 mg/m2 Carfilzomib

NCT02294357 | Terminated Phase 2

• 1 other identifier: IST-CAR-2014-100701 (20159897)
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this Phase II study is to evaluate the safety and effectiveness (good and bad effects) of carfilzomib given as a 30-minute infusion and at a dose of 70 mg/m2 to treat patients with multiple myeloma (MM), who are currently showing progressive disease (worsening) and had progressed (did not respond to treatment) within 8 weeks of receiving treatment with twice weekly 27mg/m2 of carfilzomib. Carfilzomib is approved by the U.S. Food and Drug Administration (FDA) to be used only in certain U.S. patients with relapsed and refractory multiple myeloma that have tried and failed other therapies. Carfilzomib is considered an investigational drug for this study because the dose and regimen included in this study are different from the FDA approved carfilzomib regimen. Carfilzomib is a type of drug called a proteasome inhibitor. Carfilzomib is thought to work by preventing breakdown of abnormal proteins in cells, causing the cells to die. Cancer cells are more sensitive to these effects than normal cells. Carfilzomib has been previously given to more than 1800 people in clinical trials.

Conditions

Multiple Myeloma

Keywords

carfilzomib; proteasome inhibitor; multiple myeloma; relapsed/refractory

Outcome Measures

Primary Outcomes (3)

• Overall response rate (ORR)

  Complete response (CR)+ very good partial response (VGPR) + partial response (PR), defined using International Myeloma Working Group (IMWG) criteria

  up to 30 months

• Clinical Benefit Rate (CBR)

  CBR=ORR + minor response (MR)

  up to 30 months

• Number of patients undergoing adverse events

  Adverse events (AEs) graded via the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria

  up to 36 months

Secondary Outcomes (5)

• Time to Progression (TTP)

  36 months

• Progression-Free Survival (PFS)

  36 months

• Time to Response (TTR)

  36 months

• Duration of Response (DOR)

  36 months

• Overall Survival (OS)

  36 months

Study Arms (5)

Carfilzomib + Dexamethasone

EXPERIMENTAL

Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dexamethasone (IV or PO) will be given prior to each carfilzomib administration.

Drug: Carfilzomib; Drug: Dexamethasone

Carfilzomib + Prednisone

EXPERIMENTAL

Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Prednisone (IV or PO) will be given prior to each carfilzomib administration.

Drug: Carfilzomib; Drug: Prednisone

Carfilzomib + Methylprednisolone

EXPERIMENTAL

Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Methylprednisolone(IV or PO) will be given prior to each carfilzomib administration.

Drug: Carfilzomib; Drug: Methylprednisolone

Carfilzomib+Lenalidomide+Dexamethasone

EXPERIMENTAL

Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dexamethasone (IV or PO) will be given prior to each carfilzomib administration. Lenalidomide will be given at the same dose and schedule as patient was receiving previously.

Drug: Carfilzomib; Drug: Dexamethasone; Drug: Lenalidomide

Carfilzomib+Pomalidomide+Dexamethasone

EXPERIMENTAL

Carfilzomib will be administered at 70 mg/m2 as an infusion over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dexamethasone (IV or PO) will be given prior to each carfilzomib administration. Pomalidomide will be given PO at 4mg daily on days 1-21 of a 28-day cycle

Drug: Carfilzomib; Drug: Dexamethasone; Drug: Pomalidomide

Interventions

Carfilzomib DRUG

Also known as: Kyprolis

Carfilzomib + Dexamethasone; Carfilzomib + Methylprednisolone; Carfilzomib + Prednisone; Carfilzomib+Lenalidomide+Dexamethasone; Carfilzomib+Pomalidomide+Dexamethasone

Dexamethasone DRUG

If the patient was receiving steroids at the equivalent of \> 8 mg of dexamethasone weekly either intravenously (IV) or Per Orem (PO) in combination with carfilzomib, the same drug(s), dose(s) and schedule(s) of steroids will be continued. If the patient was not receiving steroids or was receiving less than the equivalent of 8 mg of dexamethasone weekly, then he/she will be given 8 mg of dexamethasone (IV or PO) prior to each carfilzomib administration.

Also known as: Decadron, Dexamethasone acetate

Carfilzomib + Dexamethasone; Carfilzomib+Lenalidomide+Dexamethasone; Carfilzomib+Pomalidomide+Dexamethasone

Prednisone DRUG

f the patient was receiving prednisone, at the equivalent of \> 8 mg of dexamethasone weekly PO in combination with carfilzomib, he/she will continue to receive prednisone at the same dose and schedule.

Also known as: Deltasone, Cortan

Carfilzomib + Prednisone

Methylprednisolone DRUG

If the patient was receiving methylprednisolone at the equivalent of \> 8 mg of dexamethasone weekly either IV or PO in combination with carfilzomib, he/she will continue to receive methylprednisolone at the same dose and schedule.

Also known as: Medrol, Methylprednisolone acetate

Carfilzomib + Methylprednisolone

Lenalidomide DRUG

given at same dose and schedule as patient was receiving while being treated with twice weekly carfilzomib at 27 mg/m2

Also known as: Revlimid

Carfilzomib+Lenalidomide+Dexamethasone

Pomalidomide DRUG

administered PO at 4mg daily on days 1-21 of a 28 day cycle

Also known as: Pomalyst

Carfilzomib+Pomalidomide+Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Has a diagnosis of MM based on standard criteria as follows:
• Major criteria:
• Plasmacytomas on tissue biopsy.
• Bone marrow plasmacytosis (greater than 30% plasma cells).
• Monoclonal immunoglobulin (Ig) spike on serum electrophoresis IgG greater than 3.5 g/dL or IgA greater than 2.0 g/dL; kappa or lambda light chain excretion greater than 1 g/day on 24-hour urine protein electrophoresis.
• Minor criteria:
• bone marrow plasmacytosis (10% to 30% plasma cells)
• monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
• lytic bone lesions
• normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600 mg/dL
• Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:
• any 2 of the major criteria
• major criterion 1 plus minor criterion 2, 3, or 4
• major criterion 3 plus minor criterion 1 or 3
• minor criteria 1, 2, and 3, or 1, 2, and 4

You may not qualify if:

• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia (\> 2.0 × 109/L circulating plasma cells by standard differential)
• Waldenström's macroglobulinemia
• Amyloidosis
• Glucocorticoid therapy (prednisone \> 30 mg/day or equivalent) within 7 days prior to first dose
• Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to first dose
• Treatment with bortezomib (Velcade®), thalidomide, pomalidomide (Pomalyst®) or lenalidomide (Revlimid®) within 21 days prior to first dose
• Focal radiation therapy within 7 days prior to first dose. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (i.e., prior radiation must have been to \< 30% of the bone marrow)
• Immunotherapy within 21 days prior to first dose
• Major surgery within 21 days prior to first dose
• Active congestive heart failure (New York Heart Association \[NYHA\] Classes III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to first dose. Echocardiogram or MUGA evidence of left ventricular ejection fraction (LVEF) below institutional normal within 28 days prior to enrollment
• Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at HBV), or antifungal agents within 14 days prior to first dose
• Known human immunodeficiency virus (HIV) seropositivity
• Known active hepatitis B or C virus infection (except for patients with HBV receiving and responding to HBV antiviral therapy: these patients are allowed)
• Patients with known cirrhosis

Sponsors & Collaborators

• Oncotherapeutics: lead
• Amgen: collaborator

Study Sites (7)

California Cancer Associates for Research & Excellence (cCARE)

Encinitas, California, 92024, United States

Location

Wellness Oncology and Hematology

West Hills, California, 91307, United States

Location

James R Berenson, MD, Inc.

West Hollywood, California, 90069, United States

Location

Cancer Specialists of North Florida

Fleming Island, Florida, 32003, United States

Location

Hudson Valley Hem/Onc Associates

Poughkeepsie, New York, 12601, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Blood & Cancer Center of East Texas

Tyler, Texas, 75701, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

carfilzomib; Dexamethasone; Calcium Dobesilate; dexamethasone acetate; Prednisone; Methylprednisolone; Methylprednisolone Acetate; Lenalidomide; pomalidomide

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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; Pregnadienediols; Prednisolone; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• James R Berenson, MD

  James R. Berenson MD, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: November 19, 2014
• Study Start: December 1, 2014
• Primary Completion: September 21, 2020
• Study Completion: September 22, 2020
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)