Multiple Myeloma-Light Chain OnlyPhase 1/2NCT01946152
Pomalidomide, Dexamethasone, and Filgrastim-sndz in Treating Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1/2 study testing Dexamethasone, Filgrastim-sndz and Laboratory Biomarker Analysis in people with Multiple Myeloma-Light Chain Only and Recurrent Plasma Cell Myeloma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I/II trial studies the side effects and the best dose of pomalidomide when given together with dexamethasone and filgrastim-sndz and to see how well they work in treating patients with multiple myeloma that has returned or that does not respond to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma-Light Chain Only, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- What is being tested?
- Dexamethasone, Filgrastim-sndz and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Mar 2014to 18 Mar 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Relapsed and/or refractory multiple myeloma with measurable disease, as defined by one or both of the following (assessed within 14 days prior to initiation of therapy): a) serum myeloma protein (M-protein) >= 0.5 g/d; b) urine Bence-Jones protein >= 200 mg/24 hours
- Patients with light chain only myeloma are eligible; the involved free light chain level >= 100 mg/L with abnormal serum free light chain ratio
- Patients must have prior treatment with >= 2 cycles of lenalidomide and >= 2 cycles of bortezomib (either in separate regimens or as part of the same regimen) (primary refractory of subjects refractory to the most recent regimen are eligible)
- The patient has received =< 5 lines of prior therapy
- Eastern Cooperative Oncology Group performance status 0 - 2
- Serum alanine aminotransferase (ALT) < 3.5 times the upper limit of normal within 7 days of time of consent
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- Serum direct bilirubin < 2 mg/dL (34 Omol/L) within 7 days of time of consent
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L within 7 days of time of consent, without granulocyte- colony stimulating factor (G-CSF)
- Hemoglobin > 9 g/dL (80 g/L) within 7 days of time of consent (subjects may be receiving red blood cell transfusions in accordance with institutional guidelines)
- Platelet count > 100 x 10^9/L
- Creatinine clearance > 50 mL/minute within 7 days of time of consent, either measured or calculated using a standard formula (e.g., Cockcroft and Gault)
- Written informed consent in accordance with federal, local, and institutional guidelines
- All study participants must be registered into the mandatory POMALYST (pomalidomide) Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of the POMALYST REMS program
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide; FCBP must also agree to ongoing pregnancy testing and follow pregnancy testing requirements as outlined in the POMALYST REMS program; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
Who cannot join
- Hypersensitivity to previous lenalidomide or thalidomide
- History of serious allergic reactions to pegfilgrastim or filgrastim
- Chemotherapy (approved or investigational) within 3 weeks prior to signing consent
- Antibody therapy within 6 weeks prior to signing consent
- Radiotherapy to >= 3 sites at the same time within 1 week prior to signing consent
- Immunotherapy within 28 days prior to signing consent
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- Pregnant or breast feeding females
- Major surgery within 21 days prior to signing consent
- Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to signing consent
- Known human immunodeficiency virus infection
- Known active hepatitis B or C infection
- Unstable angina or myocardial infarction within 4 months prior to registration, 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
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to signing consent
- 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 signing consent
- Subjects with known or likely systemic amyloidosis
- Ongoing graft-vs-host disease
- 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.
About this study
Official title: A Phase I/II Study of Pomalidomide and Dexamethasone With Growth Factor Support in Patients With Relapsed/Refractory Multiple Myeloma
This phase I/II trial studies the side effects and the best dose of pomalidomide when given together with dexamethasone and filgrastim-sndz and to see how well they work in treating patients with multiple myeloma that has returned or that does not respond to treatment. Pomalidomide may stimulate or suppress the immune system in different ways and may stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, 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. Colony-stimulating factors, such as filgrastim-sndz, may increase the production of red and white blood cells and may help the immune system recover from the side effects of pomalidomide and/or dexamethasone. Giving pomalidomide together with dexamethasone and filgrastim-sndz may work better in treating patients with multiple myeloma.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of pomalidomide and dexamethasone when given with growth factor support in patients with relapsed and refractory multiple myeloma. (Phase I) II. To evaluate the safety of pomalidomide and dexamethasone at the MTD. (Phase II)
SECONDARY OBJECTIVES:
- To obtain preliminary estimates of the anti-myeloma activity of higher doses of pomalidomide given with low dose dexamethasone and growth factor support in patients with relapsed and refractory multiple myeloma.
II. Activity will be defined by the overall response rate (ORR); (partial response [PR] or better) and clinical benefit response (CBR) rate (minor response [MR] or better), as well as by the response durability (duration of response [DOR], progression-free survival [PFS], and time to progression [TTP]).
III. To further evaluate the safety of pomalidomide and dexamethasone at the maximum tolerated dose (MTD).
EXPLORATORY OBJECTIVES:
- To examine the influence of cereblon expression and activation of the wingless-type (Wnt)/beta-catenin pathway on the activity of high dose pomalidomide with low dose dexamethasone.
OUTLINE: This is a phase I, dose-escalation study of pomalidomide followed by a phase II study.
INDUCTION: Patients receive pomalidomide orally (PO) daily on days 1-21, dexamethasone PO on days 1, 8, 15, and 22, and filgrastim-sndz subcutaneously (SC) on days 22-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive lower-dose pomalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.
- Conditions
- Multiple Myeloma-Light Chain Only, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Being tested
- Dexamethasone, Filgrastim-sndz, Laboratory Biomarker Analysis, Pomalidomide
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO
Filgrastim-sndzBiological
Also called Filgrastim Biosimilar Filgrastim-sndz, Zarxio
Given SC
Laboratory Biomarker AnalysisOther
Correlative studies
PomalidomideDrug
Also called 4-Aminothalidomide, Actimid, CC-4047, Imnovid
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pomalidomide, dexamethasone, filgrastim-sndz) | Experimental | INDUCTION: Patients receive pomalidomide PO daily on days 1-21, dexamethasone PO on days 1, 8, 15, and 22, and filgrastim-sndz SC on days 22-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive lower-dose pomalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Dexamethasone; Biological: Filgrastim-sndz; Other: Laboratory Biomarker Analysis; Drug: Pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) (Phase I)
Safety and tolerability will be assessed by clinical review of all relevant parameters, including dose limiting toxicities. Toxicity type and severity will be summarized by frequency tables. Maximum tolerated dose defined as the highest dose level in which patients have been treated with less than 2 instances of dose-limiting toxicity (Phase I)
Measured: 28 days
Number of Participants Recommended Phase II Dose of Pomalidomide and Dexamethasone, When Both Agents Are Administered Together With Granulocyte-colony Stimulating Factor (Filgrastim) (Phase I)
Measured: Up to 28 days
Secondary outcomes (2)
Number of Participants With Best Overall Response Defined Using the International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
Per International Myeloma Working Group Uniform Response Criteria (IMWG-URC): Complete Response (CR), Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow; Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein <100 mg/24 hours; Partial Response (PR), > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h; Stable Disease (SD) = CR + PR.
Measured: After 112 days (4 courses) of therapy
Number of Participants With Progression-free Survival
Measured: Up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2013 (estimated)
- Study start5 Mar 2014
- Primary completion18 Mar 2020
- Study completion18 Mar 2020
Why it stopped: Per PI at time of CR
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple Myeloma-Light Chain OnlyStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
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
- Luhua (Michael) Wang, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01946152
- Sponsor's protocol ID
- 2013-0018
- Other IDs
- NCI-2014-01270, NCI-2014-00159, 2013-0018
- Status last verified
- Jul 2021
- First submitted
- 16 Sep 2013
- Last updated
- 30 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- 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 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Pomalidomide and Dexamethasone With Growth Factor Support in Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01946152
- Acronym / sponsor ID
- 2013-0018
- Conditions
- Multiple Myeloma-Light Chain Only, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Per PI at time of CR
- Enrolment
- 21 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 5 Mar 2014 (actual)
- Primary completion
- 18 Mar 2020 (actual)
- Study completion
- 18 Mar 2020 (actual)
- First posted
- 19 Sep 2013 (estimated)
- Results
- Posted 30 Jul 2021
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/II trial studies the side effects and the best dose of pomalidomide when given together with dexamethasone and filgrastim-sndz and to see how well they work in treating patients with multiple myeloma that has returned or that does not respond to treatment. Pomalidomide may stimulate or suppress the immune system in different ways and may stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, 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. Colony-stimulating factors, such as filgrastim-sndz, may increase the production of red and white blood cells and may help the immune system recover from the side effects of pomalidomide and/or dexamethasone. Giving pomalidomide together with dexamethasone and filgrastim-sndz may work better in treating patients with multiple myeloma.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of pomalidomide and dexamethasone when given with growth factor support in patients with relapsed and refractory multiple myeloma. (Phase I) II. To evaluate the safety of pomalidomide and dexamethasone at the MTD. (Phase II)
SECONDARY OBJECTIVES:
- To obtain preliminary estimates of the anti-myeloma activity of higher doses of pomalidomide given with low dose dexamethasone and growth factor support in patients with relapsed and refractory multiple myeloma.
II. Activity will be defined by the overall response rate (ORR); (partial response [PR] or better) and clinical benefit response (CBR) rate (minor response [MR] or better), as well as by the response durability (duration of response [DOR], progression-free survival [PFS], and time to progression [TTP]).
III. To further evaluate the safety of pomalidomide and dexamethasone at the maximum tolerated dose (MTD).
EXPLORATORY OBJECTIVES:
- To examine the influence of cereblon expression and activation of the wingless-type (Wnt)/beta-catenin pathway on the activity of high dose pomalidomide with low dose dexamethasone.
OUTLINE: This is a phase I, dose-escalation study of pomalidomide followed by a phase II study.
INDUCTION: Patients receive pomalidomide orally (PO) daily on days 1-21, dexamethasone PO on days 1, 8, 15, and 22, and filgrastim-sndz subcutaneously (SC) on days 22-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive lower-dose pomalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months 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 (pomalidomide, dexamethasone, filgrastim-sndz) | Experimental | Drug: Dexamethasone, Biological: Filgrastim-sndz, Other: Laboratory Biomarker Analysis, Drug: PomalidomideINDUCTION: Patients receive pomalidomide PO daily on days 1-21, dexamethasone PO on days 1, 8, 15, and 22, and filgrastim-sndz SC on days 22-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lower-dose pomalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Relapsed and/or refractory multiple myeloma with measurable disease, as defined by one or both of the following (assessed within 14 days prior to initiation of therapy): a) serum myeloma protein (M-protein) >= 0.5 g/d; b) urine Bence-Jones protein >= 200 mg/24 hours
- Patients with light chain only myeloma are eligible; the involved free light chain level >= 100 mg/L with abnormal serum free light chain ratio
- Patients must have prior treatment with >= 2 cycles of lenalidomide and >= 2 cycles of bortezomib (either in separate regimens or as part of the same regimen) (primary refractory of subjects refractory to the most recent regimen are eligible)
- The patient has received =< 5 lines of prior therapy
- Eastern Cooperative Oncology Group performance status 0 - 2
Key exclusion criteria (18 listed)
- Hypersensitivity to previous lenalidomide or thalidomide
- History of serious allergic reactions to pegfilgrastim or filgrastim
- Chemotherapy (approved or investigational) within 3 weeks prior to signing consent
- Antibody therapy within 6 weeks prior to signing consent
- Radiotherapy to >= 3 sites at the same time within 1 week prior to signing consent
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 |
|---|---|---|
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO | Drug | Treatment (pomalidomide, dexamethasone, filgrastim-sndz) |
| Filgrastim-sndzAlso: Filgrastim Biosimilar Filgrastim-sndz, ZarxioGiven SC | Biological | Treatment (pomalidomide, dexamethasone, filgrastim-sndz) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pomalidomide, dexamethasone, filgrastim-sndz) |
| PomalidomideAlso: 4-Aminothalidomide, Actimid, CC-4047, ImnovidGiven PO | Drug | Treatment (pomalidomide, dexamethasone, filgrastim-sndz) |
Primary outcome
Maximum Tolerated Dose (MTD) (Phase I)
Time frame: 28 days
Safety and tolerability will be assessed by clinical review of all relevant parameters, including dose limiting toxicities. Toxicity type and severity will be summarized by frequency tables. Maximum tolerated dose defined as the highest dose level in which patients have been treated with less than 2 instances of dose-limiting toxicity (Phase I)
Number of Participants Recommended Phase II Dose of Pomalidomide and Dexamethasone, When Both Agents Are Administered Together With Granulocyte-colony Stimulating Factor (Filgrastim) (Phase I)
Time frame: Up to 28 days
2 secondary outcomes
Number of Participants With Best Overall Response Defined Using the International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
Time frame: After 112 days (4 courses) of therapy
Number of Participants With Progression-free Survival
Time frame: Up to 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Luhua (Michael) Wang 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 1/2 study testing Dexamethasone, Filgrastim-sndz and Laboratory Biomarker Analysis in people with Multiple Myeloma-Light Chain Only 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 14 inclusion and 18 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 30 Jul 2021. 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 30 Jul 2021). 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?
Maximum Tolerated Dose (MTD) (Phase I) (time frame: 28 days). 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?
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 30 Jul 2021.