Plasma Cell LeukemiaPhase 1NCT01372540
Filanesib and Carfilzomib in Treating Patients With Relapsed or Refractory Multiple Myeloma or Plasma Cell Leukemia
A Phase 1 study testing Carfilzomib, Filanesib and Laboratory Biomarker Analysis in people with Plasma Cell Leukemia and Recurrent Plasma Cell Myeloma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of filanesib when given together with carfilzomib in treating patients with multiple myeloma or plasma cell leukemia that has returned or does not respond to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Plasma Cell Leukemia, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- What is being tested?
- Carfilzomib, Filanesib and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Feb 2012to 16 May 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Confirmed relapsed or refractory multiple myeloma (MM) or plasma cell leukemia (PCL); patients should have received at least 1 prior treatment regimen; prior treatment must have included at least one full cycle of a proteasome inhibitor (e.g., bortezomib) and at least one full cycle of an immunomodulatory (IMiD) (e.g., thalidomide, lenalidomide or pomalidomide); patients who have had prior ARRY-520 and carfilzomib will be allowed in the dose escalation phase, however prior ARRY-520 and carfilzomib will be excluded in the dose expansion cohort 1 of part A; there will be 2 cohorts in the dose expansion of part A: cohort 1 will be patients who are carfilzomib sensitive; cohort 2 will be patients who are carfilzomib refractory
- Part B: For Part B dose-expansion: once a MTD has been established in part A, additional dose escalation will occur with subsequent dose escalation of carfilzomib; during the dose escalation of part B, patient (pt) must have at least 1 line of prior therapy and no limitations on prior therapy; patients who had prior clinical benefit/response to ARRY-520 or carfilzomib with a stable disease (SD) or better may be eligible for dose expansion of part B; dose expansion of part B will be patients who are carfilzomib sensitive
- 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
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- Patients with oligo- or non-secretory disease must have bone marrow involvement with at least 30% plasmacytosis
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 75 x 10^9/L; if the bone marrow contains >= 50% plasma cells, a platelet count of >= 50 x 10^9/L is allowed
- Left ventricular ejection fraction (LVEF) >= 40%; 2-dimensional (D) transthoracic echocardiogram (ECHO) is the preferred method of evaluation; multigated acquisition scan (MUGA) is acceptable if ECHO is not available
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamate pyruvic transaminase (SGPT) =< 2.5 x the upper limit of normal (ULN)
- Bilirubin < 2.0 mg/dL
- Serum creatinine =< 2.5 mg/dL or a calculated creatinine clearance of at least 50 mL/min (using the Cockcroft and Gault method)
- Female patients who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, (those who are post-menopausal for less than 1 year) must have negative serum or urine pregnancy test and agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
- Male patients, even if surgically sterilized (i.e., status postvasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, OR
- Agree to completely abstain from heterosexual intercourse
- Understand and voluntarily signed informed consent
Who cannot join
- Primary amyloidosis
- Treatment with an investigational product or device within 21 days of cycle 1 day 1
- History of allergic reaction/hypersensitivity to any of the study medications, their analogues or excipients in the various formulations
- Cytotoxic therapy or monoclonal antibodies within 21 days prior to cycle 1 day 1
- 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
- Major surgery within 14 days and minor surgery within 7 days prior to cycle 1 day 1
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- Corticosteroid doses > 10 mg/day of prednisone or equivalent within 14 days prior to cycle 1 day 1
- Medical, psychiatric, cognitive or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study or, in the judgment of the investigator, would make the patient inappropriate for study participation
- Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
- 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
- Patients who are eligible for autologous transplantation
- Active congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention
- Myocardial infarction within four months prior to enrollment
- Lactating women
- Patients with known human immunodeficiency virus (HIV) seropositivity
- Patients with active clinical infections
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of Arry-520 and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma
This phase I trial studies the side effects and best dose of filanesib when given together with carfilzomib in treating patients with multiple myeloma or plasma cell leukemia that has returned or does not respond to treatment. Drugs used in chemotherapy, such as filanesib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving filanesib together with carfilzomib may be a better treatment for multiple myeloma or plasma cell leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety and the maximum-tolerated dose (MTD) of filanesib (ARRY-520) when combined with carfilzomib.
SECONDARY OBJECTIVES:
- To obtain preliminary estimates of the efficacy of ARRY-520 when combined with carfilzomib.
II. To explore potential markers for patient selection and obtain a preliminary assessment of the biological activity of ARRY-520 when combined with carfilzomib.
OUTLINE: This is a dose-escalation study.
Patients receive filanesib intravenously (IV) over 1 hour on days 1, 2, 15, and 16 and carfilzomib IV over 10-30 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After 8 courses of therapy, patients may continue with dosing of carfilzomib on days 1, 2, 15, and 16 and filanesib as tolerated. If patient progresses on carfilzomib maintenance with administration on days 1, 2, 15, and 16 they may increase the intensity and add in days 8 and 9 dosing.
After completion of study treatment, patients are followed up within 30 days and then periodically thereafter.
- Being tested
- Carfilzomib, Filanesib, Laboratory Biomarker Analysis
- Medical subject headings
- Leukemia, Plasma Cell, 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
FilanesibDrug
Also called ARRY-520, ARRY520
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (filanesib and carfilzomib) | Experimental | Patients receive filanesib IV over 1 hour on days 1, 2, 15, and 16 and carfilzomib IV over 10-30 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After 8 courses of therapy, patients may continue with dosing of carfilzomib on days 1, 2, 15, and 16 and filanesib as tolerated. If patient progresses on carfilzomib maintenance with administration on days 1, 2, 15, and 16 they may increase the intensity and add in days 8 and 9 dosing. Receives: Drug: Carfilzomib; Drug: Filanesib; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of study treatment, defined as the dose level below the dose inducing dose limiting toxicity in >= 33% of the patients and will be the recommended dose level for the expansion
Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2011 (estimated)
- Study start24 Feb 2012
- Primary completion16 May 2019
- Study completion16 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Plasma Cell LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Robert Orlowski, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01372540
- Sponsor's protocol ID
- 2011-0144
- Other IDs
- NCI-2011-01120, 2011-0144, P30CA016672
- Status last verified
- Jul 2019
- First submitted
- 10 Jun 2011
- Last updated
- 16 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Arry-520 and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01372540
- Acronym / sponsor ID
- 2011-0144
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 24 Feb 2012 (actual)
- Primary completion
- 16 May 2019 (actual)
- Study completion
- 16 May 2019 (actual)
- First posted
- 14 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of filanesib when given together with carfilzomib in treating patients with multiple myeloma or plasma cell leukemia that has returned or does not respond to treatment. Drugs used in chemotherapy, such as filanesib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving filanesib together with carfilzomib may be a better treatment for multiple myeloma or plasma cell leukemia.
Detailed description
PRIMARY OBJECTIVES:
- To determine the safety and the maximum-tolerated dose (MTD) of filanesib (ARRY-520) when combined with carfilzomib.
SECONDARY OBJECTIVES:
- To obtain preliminary estimates of the efficacy of ARRY-520 when combined with carfilzomib.
II. To explore potential markers for patient selection and obtain a preliminary assessment of the biological activity of ARRY-520 when combined with carfilzomib.
OUTLINE: This is a dose-escalation study.
Patients receive filanesib intravenously (IV) over 1 hour on days 1, 2, 15, and 16 and carfilzomib IV over 10-30 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After 8 courses of therapy, patients may continue with dosing of carfilzomib on days 1, 2, 15, and 16 and filanesib as tolerated. If patient progresses on carfilzomib maintenance with administration on days 1, 2, 15, and 16 they may increase the intensity and add in days 8 and 9 dosing.
After completion of study treatment, patients are followed up within 30 days and then periodically thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (filanesib and carfilzomib) | Experimental | Drug: Carfilzomib, Drug: Filanesib, Other: Laboratory Biomarker AnalysisPatients receive filanesib IV over 1 hour on days 1, 2, 15, and 16 and carfilzomib IV over 10-30 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After 8 courses of therapy, patients may continue with dosing of carfilzomib on days 1, 2, 15, and 16 and filanesib as tolerated. If patient progresses on carfilzomib maintenance with administration on days 1, 2, 15, and 16 they may increase the intensity and add in days 8 and 9 dosing. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Confirmed relapsed or refractory multiple myeloma (MM) or plasma cell leukemia (PCL); patients should have received at least 1 prior treatment regimen; prior treatment must have included at least one full cycle of a proteasome inhibitor (e.g., bortezomib) and at least one full cycle of an immunomodulatory (IMiD) (e.g., thalidomide, lenalidomide or pomalidomide); patients who have had prior ARRY-520 and carfilzomib will be allowed in the dose escalation phase, however prior ARRY-520 and carfilzomib will be excluded in the dose expansion cohort 1 of part A; there will be 2 cohorts in the dose expansion of part A: cohort 1 will be patients who are carfilzomib sensitive; cohort 2 will be patients who are carfilzomib refractory
- Part B: For Part B dose-expansion: once a MTD has been established in part A, additional dose escalation will occur with subsequent dose escalation of carfilzomib; during the dose escalation of part B, patient (pt) must have at least 1 line of prior therapy and no limitations on prior therapy; patients who had prior clinical benefit/response to ARRY-520 or carfilzomib with a stable disease (SD) or better may be eligible for dose expansion of part B; dose expansion of part B will be patients who are carfilzomib sensitive
- Measurable MM disease, defined as one of the following:
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
Key exclusion criteria (16 listed)
- Primary amyloidosis
- Treatment with an investigational product or device within 21 days of cycle 1 day 1
- History of allergic reaction/hypersensitivity to any of the study medications, their analogues or excipients in the various formulations
- Cytotoxic therapy or monoclonal antibodies within 21 days prior to cycle 1 day 1
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarfilzomibAlso: Kyprolis, PR-171Given IV | Drug | Treatment (filanesib and carfilzomib) |
| FilanesibAlso: ARRY-520, ARRY520Given IV | Drug | Treatment (filanesib and carfilzomib) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (filanesib and carfilzomib) |
Primary outcome
Maximum tolerated dose of study treatment, defined as the dose level below the dose inducing dose limiting toxicity in >= 33% of the patients and will be the recommended dose level for the expansion
Time frame: 28 days
Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2019.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Orlowski principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carfilzomib, Filanesib and Laboratory Biomarker Analysis in people with Plasma Cell Leukemia and Recurrent Plasma Cell Myeloma, run by M.D. Anderson Cancer Center 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 22 inclusion and 16 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: finished, as of the sponsor's last update on 16 Jul 2019. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose of study treatment, defined as the dose level below the dose inducing dose limiting toxicity in >= 33% of the patients and will be the recommended dose level for the expansion (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jul 2019.