Carfilzomib and Stem Cell Transplant for Plasma Cell Myeloma

NCT01658904 | Terminated Phase 1 Results

• 2 other identifiers: 12017912-C-0179
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Plasma cell myeloma is a type of cancer that affects the plasma cells in the bone marrow. It can be difficult to treat with chemotherapy. One possible treatment combines chemotherapy with a stem cell transplant. To make this treatment more effective, researchers want to give another drug along with the transplant. This drug, carfilzomib, is often used to help treat plasma cell myeloma. However, it is not usually given along with the transplant. Researchers want to see if it is safe and effective to combine the stem cell transplant with carfilzomib, and if it improves the results of the transplant. Objectives: \- To test the safety and effectiveness of carfilzomib given with stem cell transplant for plasma cell myeloma. Eligibility: \- Individuals between 18 and 75 years of age who are having a stem cell transplant to treat plasma cell myeloma. Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and a bone marrow biopsy will also be performed.
• Participants will have their own stem cells collected for the transplant. The transplant will be performed according to the standard of care.
• All participants will receive carfilzomib on the first 2 days after transplant. The study doctors will determine the number of additional doses that they may have.
• Treatment will be monitored with frequent blood tests and imaging studies.

Conditions

Multiple Myeloma; Leukemia, Plasma Cell

Keywords

Autologous Transplant; Proteasome Inhibitor; Melphalan; Filgrastim

Outcome Measures

Primary Outcomes (2)

• Engraftment Failure Transplant Related Mortality

  Engraftment failure is defined as the failure to achieve neutrophil engraftment by day 21; defined from day 0, day of autologous hematopoietic cell transplantation (AHCT), as the first of three consecutive days on which the patient's absolute neutrophil count is greater than 0.5x10(9)/l following the nadir. Transplant related mortality is defined as any subject who dies in the first 100 days post-AHCT of any non-relapse related cause.

  up to day 100

• Number of Participants With Adverse Events

  Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

  8 months and 15 days

Secondary Outcomes (2)

• Evaluate the Immune Reconstitution Post-Pre-autologous Hematopoietic Cell Transplantation (AHCT) Following Carfilzomib (CFZ) Therapy

  Post-AHCT following CFZ therapy

• Evaluate the Effects of the Addition of Carfilzomib (CFZ) in the Early Post-Pre-autologous Hematopoietic Cell Transplantation (AHCT) Period on the Response Rate at Day 100 Post-AHCT

  Day 100 post-AHCT

Study Arms (3)

Cohort 1- CFZ 20 mg/m^2 (Day 1,2)

EXPERIMENTAL

Phase I/II study on the backbone of high-dose melphalan on day -2 pre-autologous hematopoietic cell transplantation (AHCT) •Addition of an increasing number of doses of Carfilzomib (CFZ) in the early post-AHCT period introduced in a step-wise fashion in 3 successive cohorts of 3 to 15 subjects: Cohort 1: add CFZ 20 mg/m\^2 intravenous (IV) on days +1, +2 Cohort 2 : add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9 Cohort 3: add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9 and add an early post-AHCT consolidation following engraftment: CFZ 20 mg/m\^2 IV given on days 42-43 then CFZ 56 mg/m\^2 IV given on days 49-50, 56-57, then on days 70.

Drug: Carfilzomib; Drug: Melphalan; Drug: Filgrastim

Cohort 2- CFZ 20 mg/m^2 (Day 1,2,8,9)

EXPERIMENTAL

Phase I/II study on the backbone of high-dose melphalan on day -2 pre-autologous hematopoietic cell transplantation (AHCT) •Addition of an increasing number of doses of Carfilzomib (CFZ) in the early post-AHCT period introduced in a step-wise fashion in 3 successive cohorts of 3 to 15 subjects: Cohort 1: add CFZ 20 mg/m\^2 intravenous (IV) on days +1, +2 Cohort 2 : add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9 Cohort 3: add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9 and add an early post-AHCT consolidation following engraftment: CFZ 20 mg/m\^2 IV given on days 42-43 then CFZ 56 mg/m\^2 IV given on days 49-50, 56-57, then on days 70.

Drug: Carfilzomib; Drug: Melphalan; Drug: Filgrastim

Cohort 3-CFZ 20 mg/m^2 (Day1,2,8,9/AHCT)

EXPERIMENTAL

Phase I/II study on the backbone of high-dose melphalan on day -2 pre-autologous hematopoietic cell transplantation (AHCT) •Addition of an increasing number of doses of Carfilzomib (CFZ) in the early post-AHCT period introduced in a step-wise fashion in 3 successive cohorts of 3 to 15 subjects: Cohort 1: add CFZ 20 mg/m\^2 intravenous (IV) on days +1, +2 Cohort 2 : add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9 Cohort 3: add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9 and add an early post-AHCT consolidation following engraftment: CFZ 20 mg/m\^2 IV given on days 42-43 then CFZ 56 mg/m\^2 IV given on days 49-50, 56-57, then on days 70.

Drug: Carfilzomib; Drug: Melphalan; Drug: Filgrastim

Interventions

Carfilzomib DRUG

Cohort 1- CFZ 20 mg/m^2 (Day 1,2); Cohort 2- CFZ 20 mg/m^2 (Day 1,2,8,9); Cohort 3-CFZ 20 mg/m^2 (Day1,2,8,9/AHCT)

Melphalan DRUG

Cohort 1- CFZ 20 mg/m^2 (Day 1,2); Cohort 2- CFZ 20 mg/m^2 (Day 1,2,8,9); Cohort 3-CFZ 20 mg/m^2 (Day1,2,8,9/AHCT)

Filgrastim DRUG

Cohort 1- CFZ 20 mg/m^2 (Day 1,2); Cohort 2- CFZ 20 mg/m^2 (Day 1,2,8,9); Cohort 3-CFZ 20 mg/m^2 (Day1,2,8,9/AHCT)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Multiple myeloma criteria for newly or recently diagnosed subjects
• Presence of clonal plasma cells in the bone marrow greater than or equal to 10% or a documented clonal plasmacytoma (either by immuno-histochemistry or by Ig gene rearrangement), AND
• Presence of an M-component; an M-component (immunoglobulin G (IgG) or immunoglobulin A (IgA)) in serum greater than or equal to 1g/dl or in urine greater or equal to 200 mg/24 h.
• ALTERNATIVELY, if the M-component criterion is not met:
• An abnormal serum free light chain (FLC) ratio on the serum FLC assay, or if the FLC ratio is normal,
• Baseline bone marrow must have 10% or greater clonal plasma cells
• AND, IN ADDITION, presence of one or more of the following attributable to the disease (in the presence or absence of an M-component):
• Calcium elevation greater than 11.5 mg/dl (2.65 mmol/l)
• Renal insufficiency: serum creatinine greater than 2 mg/dl (177 mmol/l) or less than 60ml/min.
• Hemoglobin less than 10 g/dl (12.5 mmol/l) or 2 g/dl (1.25 mmol/l) below lower normal
• Bone disease (lytic lesions or osteopenia)
• Other evidence of disease activity: repeated infections, secondary amyloidosis, hyperviscosity, hypogammablobulinemia
• Criteria for subjects with persistent or recurrent disease
• Subjects with recurrent or persistent disease are eligible if:
• Criteria for initiating therapy for plasma cell myeloma (PCM) had been present at the time of initiation of therapy or there is clear clinical indication for salvage therapy.

You may not qualify if:

• Karnofsky performance status of 70% or greater (Eastern Cooperative Oncology Group (ECOG) 0 or 1)
• Ejection fraction (EF) by multi-gated acquisition scan (MUGA) or 2-D echocardiogram within institution normal limits. In case of low ejection fraction (EF), the subject may remain eligible after a stress echocardiogram is performed if the EF is more than 35% and if the increase in EF with stress is estimated at 10% or more.
• creatinine clearance \> 25ml/min (measured on a 24 hour urine collection)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x upper limit of normal
• Bilirubin less than or equal to1.5 (except if due to Gilbert's disease)
• Corrected carbon dioxide diffusing capacity (DLCO) greater than or equal to 40% on pulmonary function tests
• Prior allogeneic or autologous stem cell transplantation
• History of recent (\< 6 months) cerebrovascular accident
• History of documented recent (\< 6 months) pulmonary embolus
• Clinically significant cardiac pathology:
• Myocardial infarction within 6 months prior to enrollment,
• Class III or IV heart failure according to New York Heart Association (NYHA),
• Uncontrolled angina,
• Severe uncontrolled ventricular arrhythmias, or
• Electrocardiographic evidence of acute ischemia or active conduction abnormalities felt to pose a significant cardiac riks by a Cardiology consultant

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.

  PMID: 18287387 BACKGROUND

• Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR; Eastern Cooperative Oncology Group. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006 Jan 20;24(3):431-6. doi: 10.1200/JCO.2005.03.0221. Epub 2005 Dec 19.

  PMID: 16365178 BACKGROUND

• Tosi P, Zamagni E, Cellini C, Plasmati R, Cangini D, Tacchetti P, Perrone G, Pastorelli F, Tura S, Baccarani M, Cavo M. Neurological toxicity of long-term (>1 yr) thalidomide therapy in patients with multiple myeloma. Eur J Haematol. 2005 Mar;74(3):212-6. doi: 10.1111/j.1600-0609.2004.00382.x.

  PMID: 15693790 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Leukemia, Plasma Cell

Interventions

carfilzomib; Melphalan; Filgrastim

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; Leukemia

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors

Limitations and Caveats

The study was closed prematurely because the investigator left the National Institutes of Health.

Results Point of Contact

• Title: Dr. Ronald Gress
• Organization: National Cancer Institute

gressr@dc10a.nci.nih.gov

301-496-1791

Study Officials

• Ronald E Gress, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 3, 2012
• First Posted: August 7, 2012
• Study Start: July 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: April 1, 2014
• Last Updated: June 1, 2016
• Results First Posted: February 3, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)