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Multiple MyelomaPhase 1/2NCT01658904

Carfilzomib and Stem Cell Transplant for Plasma Cell Myeloma

A Phase 1/2 study testing Carfilzomib, Melphalan and Filgrastim in people with Multiple Myeloma and Leukemia, Plasma Cell, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Multiple Myeloma, Leukemia, Plasma Cell
What is being tested?
Carfilzomib, Melphalan and Filgrastim
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
Jul 2012to Apr 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • They have not undergone an autologous transplant for the treatment of PCM
  • They have received no more than two salvage regimens for the treatment of recurrent or persistent PCM (each regimen may include more than one cycle)
  • Other eligibility criteria
  • -Age > 18 years and less than or equal to 75 years.
  • In subjects between 65 and 75 years of age, physiologic age and co-morbidity will be thoroughly evaluated before enrolling. Specifically, any history of cardiovascular pathology or symptoms not clearly fitting the exclusion criteria of Section 2.1.2 will prompt an evaluation by a Clinical Center Cardiologist and eligibility will be considered on a case-by-case basis.
  • 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

Who cannot join

  • Prior allogeneic or autologous stem cell transplantation
  • Prior treatment with Carfilzomib (CFZ) is not an exclusion
  • 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,
Show all 23Show fewer
  • 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
  • Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.
  • Human immunodeficiency virus (HIV) seropositive
  • Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment
  • Active hepatitis B or C infection
  • Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
  • Major surgery within 21 days prior to enrollment
  • Non-hematologic 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
  • Significant neuropathy (Grades 3 4, or Grade 2 with pain) within 14 days prior to randomization
  • Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize CFZ)
  • Patients known or found to be pregnant
  • Female patients of childbearing age who are unwilling to practice contraception
  • Patients may be excluded at the discretion of the principal investigator (PI) if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.
  • Patients must be able to give informed consent

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Phase I / II Study Of Carfilzomib (CFZ) Intensification Early After Autologous Transplantation (AHCT) For Plasma Cell Myeloma

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.
Read more

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.
Read the detailed description

Background:

  • Despite very significant progress in therapy for plasma cell myeloma (PCM) in the last decade, the disease remains mostly incurable.
  • High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) continues to be a critical component of early treatment for PCM, but it is clear that the disease is not eradicated by the present high-dose therapy strategy, while intensifying the preparative regimen has, to this day, resulted in either no improvement in disease control or increased toxicity.
  • Carfilzomib (CFZ) is a newer proteasome inhibitor with increased activity and a safer toxicity profile than bortezomib in PCM. The favorable toxicity profile makes it a likely candidate for increasing anti-PCM drug exposure in the early post-AHCT period.

Objectives:

Primary Objectives

-Evaluate feasibility and toxicity of an increasing number of doses of CFZ administered in the early period post-AHCT for PCM

Secondary Objective

  • Evaluate the immune reconstitution post-AHCT following CFZ therapy
  • Evaluate the effects of the addition of CFZ in the early post-AHCT period on the response rate at day 100 post-AHCT

Eligibility:

  • Newly diagnosed subjects with PCM following induction therapy
  • Subjects with documentation of persistent/refractory disease who have received no more than 2 salvage regimens following relapse and who have not undergone AHCT
  • Adequate organ functions with no major co-morbidity
  • Age greater than 18 years and less than or equal to 75 years

Design:

  • Phase I/II study on the backbone of high-dose melphalan on day -2 pre-AHCT
  • Addition of an increasing number of doses of 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 on days +1, +2

Cohort 2 : add CFZ 20 mg/m^2 on days: +1, +2, +8, +9

Cohort 3: add CFZ 20 mg/m^2 on days: +1, +2, +8, +9 and add an early post-AHCT consolidation following

engraftment: CFZ 20 mg/m^2 given on days 42-43 then CFZ 56 mg/m^2 given on days 49-50, 56-57, then on days 70-71, 77-78 and 84-85

-Dose-limiting toxicity, incidence of engraftment failure and treatment-related mortality are the objects of early stopping rules for safety purposes

Keywords
Autologous Transplant, Proteasome Inhibitor, Melphalan, Filgrastim
Medical subject headings
Multiple Myeloma, Leukemia, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01658904
Study groupRoleWhat they receive
Cohort 1- CFZ 20 mg/m^2 (Day 1,2)ExperimentalPhase 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.
Receives: Drug: Carfilzomib; Drug: Melphalan; Drug: Filgrastim
Cohort 2- CFZ 20 mg/m^2 (Day 1,2,8,9)ExperimentalPhase 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.
Receives: Drug: Carfilzomib; Drug: Melphalan; Drug: Filgrastim
Cohort 3-CFZ 20 mg/m^2 (Day1,2,8,9/AHCT)ExperimentalPhase 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.
Receives: Drug: Carfilzomib; Drug: Melphalan; Drug: Filgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: up to day 100

  2. 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.

    Measured: 8 months and 15 days

Secondary outcomes (2)

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

    Measured: Post-AHCT following CFZ therapy

  2. 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

    Measured: Day 100 post-AHCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionFeb 2014
  4. Study completionApr 2014

Why it stopped: study closed prematurely because investigator left National Institutes of Health

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01658904
Sponsor's protocol ID
120179
Other IDs
12-C-0179
Status last verified
Apr 2016
First submitted
3 Aug 2012
Last updated
1 Jun 2016
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 18287387

  • 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.

    PubMed 16365178

  • 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.

    PubMed 15693790

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carfilzomib, Melphalan and Filgrastim in people with Multiple Myeloma and Leukemia, Plasma Cell, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Engraftment Failure Transplant Related Mortality (time frame: up to day 100). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01658904, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2016.

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