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Refractory Multiple MyelomaPhase 2NCT02020941

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

A Phase 2 study testing carfilzomib, dexamethasone and laboratory biomarker analysis in people with Refractory Multiple Myeloma, run by Attaya Suvannasankha at 1 site in United States.

Terminated

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

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Refractory Multiple Myeloma
What is being tested?
carfilzomib, dexamethasone and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Sep 2013to Apr 2016
Phase
Phase 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Patients with oligo- or non-secretory disease must have bone marrow involvement with at least 30% plasmacytosis on aspiration
  • Life expectancy >= 3 months as determined by the treating physician
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
  • Absolute neutrophil count (ANC) >= 1.0 × 10^9/L (without transfusion support and without hematological growth factor support within 2 weeks of cycle 1 day 1)
  • Platelets >= 50 × 10^9/L; if the bone marrow contains >= 50% plasma cells, a platelet count of >= 30 × 10^9/L is allowed (without transfusion support and without hematological growth factor support within 2 weeks of cycle 1 day 1)
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 2.5 × the upper limit of normal (ULN)
  • Bilirubin < 2.0 mg/dL
  • Serum creatinine =< 3.0 mg/dL or a calculated creatinine clearance of at least 15 mL/min (using the Cockcroft and Gault method)
  • Adequate cardiac function defined as left ventricular ejection fraction (LVEF) >= 40%
  • NOTE: 2-dimensional (2-D) transthoracic echocardiogram (ECHO) is the preferred method of evaluation
  • Multigated acquisition scan (MUGA) is acceptable if ECHO is not available
  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception; females are considered of childbearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
  • Male subjects must agree to practice contraception

Who cannot join

  • 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
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  • 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
  • No 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
  • No significant neuropathy (grades 3-4, or grade 2 with pain) within 14 days prior to cycle 1 day 1
  • No known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
  • No contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
  • No subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to cycle 1 day 1
  • Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Indiana University Cancer Center

    Indianapolis, Indiana, 46202

Other trials in United States

About this study

Official title: A Phase 2 Study of Carfilzomib and Bone Metabolism in Patients With Multiple Myeloma in First Relapse or Refractory to First Line Therapy

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the overall response rate of carfilzomib after 8 cycles of treatment in patients with first-relapsed myeloma.

SECONDARY OBJECTIVES:

  1. To assess the overall response rate to single agent carfilzomib after 4 cycles of treatment.

II. To assess progression-free survival (PFS). III. To assess time to progression (TTP). IV. To assess duration of response (DOR). V. To assess toxicities.

TERTIARY OBJECTIVES:

  1. To examine the effect of carfilzomib alone or in combination with dexamethasone on the following biologic end points and their correlation with response: measurements of bone remodeling (sodium fluoride F 18 positron emission tomography [PET], serum markers of bone remodeling and the bone marrow osteoblastic and osteoclastic differentiation and function) with the measurement of disease response and proteasome activity in the bone marrow microenvironment.

II. To describe recapture of response after progression in the maintenance phase.

OUTLINE:

TREATMENT PHASE (COURSES 1-8): Patients receive carfilzomib intravenously (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 partial response (PR) also receive dexamethasone orally (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.

After completion of study treatment, patients are followed up at 30 days and then every 3 months.

Being tested
carfilzomib, dexamethasone, laboratory biomarker analysis
Medical subject headings
Multiple Myeloma

What participants receive

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

  • carfilzomibDrug

    Also called Kyprolis, PR-171

    Given IV

  • dexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, DM

    Given IV or PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02020941
Study groupRoleWhat they receive
Treatment (carfilzomib, dexamethasone)ExperimentalTREATMENT 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.
Receives: Drug: carfilzomib; Drug: dexamethasone; Other: laboratory biomarker analysis

What is being measured

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

  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).

    Measured: At 32 weeks

Secondary outcomes (5)

  1. Overall Response Rate (ORR) After 4 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).

    Measured: At 16 weeks

  2. Progression-free Survival (PFS)

    Analysis will be performed using Kaplan-Meier estimates. Time from date on treatment to date of progression for patients who progressed or date of death for patients who died without progressing. The observations of patients remaining alive and progression free were censored at date of last disease evaluation.

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

  3. Time to Progression (TTP)

    Analysis will be performed using Kaplan-Meier estimates. Time from date on treatment to date of progression. The observations of patients who died or remained alive and progression free were censored at date of death or last disease evaluation, respectively.

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

  4. Duration of Response (DOR)

    Analysis will be performed using Kaplan-Meier estimates. Time from date of first confirmed response of partial response or better to date of progression or death. Only patients who had a response of partial response or better will be included in this analysis.

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

  5. Treatment Related Adverse Events Grade 3 or Higher

    Number of unique patients who had a treatment related (possible, probable or definite) adverse events that were graded 3 or greater.

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

Timeline

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

  1. First posted25 Dec 2013 (estimated)
  2. Study startSep 2013
  3. Primary completionJan 2016
  4. Study completionApr 2016

Why it stopped: Slow accrual

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02020941
Sponsor's protocol ID
IUCRO-0414
Other IDs
NCI-2013-01771, IUCRO-0414, P30CA082709
Status last verified
Jul 2016
First submitted
19 Dec 2013
Last updated
2 Nov 2016
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing carfilzomib, dexamethasone and laboratory biomarker analysis in people with Refractory Multiple Myeloma, run by Attaya Suvannasankha 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 29 inclusion and 21 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 2 Nov 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 phase mean?

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 2 Nov 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?

Overall Response Rate (ORR) After 8 Courses of Treatment (time frame: At 32 weeks). 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 NCT02020941.

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 2 Nov 2016.

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