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Multiple Myeloma in RelapsePhase 1NCT01889420

Phase I Trial of Everolimus, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

A Phase 1 study testing Combination therapy in people with Multiple Myeloma in Relapse, run by New Mexico Cancer Research Alliance 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 study is being conducted to test the possibility that a combination of three drugs, pomalidomide and everolimus with dexamethasone, may improve patient responses when compared with use of either drug alone, with dexamethasone in refractory/relapsed multiple myeloma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma in Relapse
What is being tested?
Combination therapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
Jul 2014to Jul 2015
Phase
Phase 1
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

  • Age > 18 years
  • Relapsed or progressive multiple myeloma (MM) (Progressive Disease), defined as a 25% increase from the lowest response value in ANY of the following:
  • Serum M-protein (absolute increase ≥0.5 g/dL)
  • Urine M-protein (absolute increase of ≥200 mg/24 hours)
  • Bone marrow plasma cell percentage (≥ 10% absolute increase) in absence of measurable M-protein
  • Difference in kappa \& lambda free light chain levels (ratio must be abnormal; absolute change must be >10 mg/dL)
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  • Patients are also considered to have progressive disease when:
  • New bone or soft tissue lesions (e.g. plasmacytomas) are identified; or
  • There is an unequivocal increase in the size of previously existing lesions; or
  • The development of an otherwise unexplained serum calcium >11.5 mg/dL
  • Have received 1, but no more than 4 prior treatment regimens or lines of therapy for MM (Induction therapy followed by stem cell transplant \& consolidation/maintenance therapy will be considered as one line of therapy)
  • ECOG Performance status 0 - 2
  • Life expectancy of at least 12 weeks
  • Evaluable MM with, at least one of the following, assessed within 21 days prior to randomization:
  • Serum M-protein ≥ 0.5 g/dL, or Urine M-protein ≥ 200 mg/24 hour, or
  • In absence of detectable serum or urine M-protein, serum FLC (SFLC) > 100 mg/L (involved light chain) and/or an abnormal kappa/lamda ratio (>4:1 or <2:1), or
  • Monoclonal plasma cells in a bone marrow biopsy/aspirate of >5%
  • Adequate organ and marrow function as defined below:
  • Leukocytes ≥ 2,500/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin < 2 X ULN
  • AST(SGOT)/ALT(SPGT) ≤ 2.5 X ULN
  • Creatinine < 1.5 X ULN
  • Contraception Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for duration of study, and for 90 days after completion of therapy.
  • A female of child-bearing potential is considered to be any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • No hysterectomy or bilateral oophorectomy; or
  • Not naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  • Male patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a female of child-bearing potential.
  • No prior therapy with pomalidomide or everolimus.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Receiving any other investigational agents. Minimum 4 week "washout" period is required.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pomalidomide, everolimus, or other agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or nursing (due to the rick for congenital abnormalities and the potential of this regimen to harm nursing infants).
  • Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization.
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  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  • Plasma cell leukemia or circulating plasma cells ≥ 2 × 10^9/L.
  • Waldenstrom's Macroglobulinemia.
  • Patients with known amyloidosis.
  • Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to randomization (i.e., prior radiation must have been to less than 30% of the bone marrow).
  • Immunotherapy within 21 days prior to randomization.
  • Myelodysplastic syndrome
  • Major surgery (excluding kyphoplasty) within 28 days
  • Known cirrhosis.
  • Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days
  • Ongoing graft-vs-host disease.
  • Using CYP3A4 inhibitors such as Ketoconazole, Ritonavir, Itraconazole, Erythromycin, Clarithromycin, Nelfinavir, Fluconazole, Amiodarone, Cyclosporine, Diltiazem, nefazadone,fluvoxamine, verapamil, chloramphenicol, Indinavir or saquinavir within 7 days of treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UNM Cancer Research and Treatment Center

    Albuquerque, New Mexico, 87131

Other trials in United States

About this study

This study is being conducted to test the possibility that a combination of three drugs, pomalidomide and everolimus with dexamethasone, may improve patient responses when compared with use of either drug alone, with dexamethasone in refractory/relapsed multiple myeloma.

Read the detailed description

Given that pomalidomide is an FDA approved drug for patients with relapsed or progressive myeloma, and everolimus has been shown to have single agent activity in relapsed myeloma, it seems reasonable to combine these two active drugs in patients with relapsed/refractory disease. Given that low dose dexamethasone dramatically improved the response rate of pomalidomide, this drug will be added to the combination.

Being tested
Combination therapy
Keywords
myeloma, relapse, refractory, relapsed, pomalidomide, pomalyst, everolimus, afinitor, dexamethasone
Medical subject headings
Neoplasms, Plasma Cell, Recurrence

What participants receive

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

  • Combination therapyDrug

    Also called Pomalyst, Afinitor

    Following determination of the maximum tolerated dosages in the phase I portion of this study, all patients enrolled in the extension portion will receive the predetermined dosage combination of pomalidomide, everolimus and dexamethasone.

    Cycles will span 28 days. Dosage schedules will be:

    1. Everolimus daily for 28 days of a 28 day cycle;
    2. Pomalidomide daily for 21 days of a 28 day cycle
    3. Dexamethasone once weekly (on days 1,8,15,22) of a 28 day cycle.
Study groups in NCT01889420
Study groupRoleWhat they receive
Combination therapyExperimentalPomalidomide: 1 tablet orally, daily for 21 days of a 28 day cycle (dose per cohort) Everolimus: 1 tablet orally for 21 days of a 28 day cycle (dose as per cohort) Dexamethasone 40 mg (20 mg >75yrs) orally, days 1, 8,15, 22 of a 28 day cycle
Receives: Drug: Combination therapy

What is being measured

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

  1. Maximum Tolerated Dosage (MTD)(Phase I)

    The Maximum Tolerated Dose (MTD) will be determined by first identifying the dose level at which >= 30% of patients experience a Dose Limiting Toxicity (DLT) according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, over a 28 day cycle. DLT will be defined based on the rate of drug-related grade 3-5, non-hematological adverse events experienced within the first 4 weeks (1 cycle) for each combined dosage scheme. The MTD will be defined as one dosage level below which DLT was observed in >= 30% of patients.

    Measured: 2 years

Secondary outcomes (3)

  1. Toxicity Profile

    The toxicity profile will be described by specific adverse event rates among patients experiencing > grade 3 hematologic events (lasting >7 days) or grades 3-5 non-hematologic adverse events, according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, over a 28 day cycle. Specific events will be described as the numbers of patients experiencing them within each treatment cohort.

    Measured: 2 years

  2. Anti-tumor Effect

    Anti-tumor effect will be assessed based on serum protein electrophoresis (SPEP) of the monoclonal protein (M-protein) and plasma concentrations of K/L free light chains (FLC) after each 28-day cycle. Descriptive statistics will be used for this measurement.

    Complete response (CR): disappearance of any M-protein and FLC as measured by SPEP and/or FLC. Pre-existing plasmacytomas must have completely resolved.

    Partial response (PR): >50% reduction in M-protein and >50% reduction in the difference between involved and uninvolved FLC. Any plasmacytoma must have decreased in size by >50%.

    Stable disease: not meeting criteria for CR, PR, or progressive disease (PD). PD: >25% increase from baseline in serum or urine M-protein (serum M-protein must increase by > 0.5 gm/dl; urine M-protein must increase by >200 mg /24 hr); or development of new plasmacytomas or new lytic bone lesions; or a measurable increase in the size of these lesions; or hypercalcemia (>11.5 mg/dl) attributed to MM.

    Measured: 3.5 years

  3. Overall Response Rate (RR)

    ORR is the percentage of patients with a > Partial Response (PR). Response is assessed based on serum protein electrophoresis (SPEP) of the monoclonal protein (M-protein) and plasma concentrations of K/L free light chains (FLC) after each 28-day cycle.

    Complete response (CR): disappearance of any M-protein and FLC as measured by SPEP and/or FLC. Pre-existing plasmacytomas must have completely resolved.

    PR: >50% reduction in M-protein and >50% reduction in the difference between involved and uninvolved FLC. Any plasmacytoma must have decreased in size by >50%.

    Stable disease: not meeting criteria for CR, PR, or progressive disease (PD). PD: >25% increase from baseline in serum or urine M-protein (serum M-protein must increase by > 0.5 gm/dl; urine M-protein must increase by >200 mg /24 hr); or development of new plasmacytomas or new lytic bone lesions; or a measurable increase in the size of these lesions; or hypercalcemia (>11.5 mg/dl) attributed to MM.

    Measured: 3 years

Timeline

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

  1. First posted28 Jun 2013 (estimated)
  2. Study startJul 2014
  3. Primary completionJun 2015
  4. Study completionJul 2015

Why it stopped: Low 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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01889420
Sponsor's protocol ID
INST 1304
Status last verified
Jul 2015
First submitted
26 Jun 2013
Last updated
31 Jul 2015
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Combination therapy in people with Multiple Myeloma in Relapse, run by New Mexico Cancer Research Alliance 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 31 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 31 Jul 2015. 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?

Yes. Results are posted in the registry (first posted 31 Jul 2015). 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 Dosage (MTD)(Phase I) (time frame: 2 years). 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 NCT01889420.

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 31 Jul 2015.

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