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Plasma Cell MyelomaPhase 2NCT02880228

Pembrolizumab, Lenalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma Eligible for Stem Cell Transplant

A Phase 2 study testing Dexamethasone, Laboratory Biomarker Analysis and Lenalidomide in people with Plasma Cell Myeloma, run by Mayo Clinic at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well pembrolizumab, lenalidomide, and dexamethasone work in treating patients with newly diagnosed multiple myeloma that are eligible for stem cell transplant. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Plasma Cell Myeloma
What is being tested?
Dexamethasone, Laboratory Biomarker Analysis and Lenalidomide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
2 sitesUnited States
Study dates
16 Sep 2016to 29 Jul 2018
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

  • Diagnosis and previously untreated active multiple myeloma by International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma
  • Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelet count >= 75000/mm^3
  • Hemoglobin >= 8.0 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
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  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
  • Prior therapy for the treatment of solitary plasmacytoma is permitted, but > 7 days should have elapsed from the last day of radiation
  • NOTE: Prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate, or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator
  • Measurable disease of multiple myeloma as defined by at least ONE of the following:
  • Serum monoclonal protein >= 1.0 g/dL
  • > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
  • Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Provide written informed consent
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Willing to follow strict birth control measures as suggested by the study
  • Female patients: If they are of childbearing potential, must agree to one of the following:
  • Practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
  • Male patients: even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willing to provide consent to Institutional Review Board (IRB) number (#) 521-93 and provide research tissue and blood specimens

Who cannot join

  • Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
  • Prior cytotoxic chemotherapy or corticosteroids for the treatment of multiple myeloma
  • NOTE: Prior corticosteroid use for the treatment of non-malignant disorders is permitted
  • Diagnosed or treated for another malignancy =< 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease.
  • NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Any of the following:
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  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
  • Other concurrent chemotherapy or any ancillary therapy considered investigational
  • NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
  • Peripheral neuropathy >= grade 3 on clinical examination or grade 2 with pain during the screening period
  • Major surgery =< 14 days prior to study registration
  • Radiotherapy =< 14 days prior to registration
  • NOTE: If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of study drugs
  • Participation in any other clinical trials with other investigational agents not included in this trial, =< 21 days prior to registration
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
  • NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Active infection requiring systemic therapy
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Received a live vaccine =< 30 days of planned start of study therapy

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase 2 Trial of Pembrolizumab, Lenalidomide, and Dexamethasone for Initial Therapy of Newly Diagnosed Multiple Myeloma Eligible for Stem Cell Transplantation

This phase II trial studies how well pembrolizumab, lenalidomide, and dexamethasone work in treating patients with newly diagnosed multiple myeloma that are eligible for stem cell transplant. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide and 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. Giving pembrolizumab, lenalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the very good partial response (VGPR) or better response rate (>= VGPR) after 4 cycles of pembrolizumab added to standard doses of lenalidomide and dexamethasone, when used as initial therapy in patients with previously untreated symptomatic multiple myeloma (MM) in patients, who are considered eligible for stem cell transplantation.

SECONDARY OBJECTIVES:

  1. To determine the >= partial response (PR) rate after 4 cycles of treatment with pembrolizumab added to standard doses of lenalidomide and dexamethasone.

II. To determine the >= VGPR response rate at any time during treatment with pembrolizumab added to standard doses of lenalidomide and dexamethasone.

III. To determine the progression free survival and overall survival among patients with previously untreated symptomatic MM following treatment with the combination of pembrolizumab, lenalidomide and dexamethasone.

IV. To determine the toxicities associated with pembrolizumab added to standard doses of lenalidomide and dexamethasone in patients with previously untreated symptomatic MM.

  1. To determine the success rate of stem cell collection following initial therapy with the combination of pembrolizumab, lenalidomide and dexamethasone in patients with newly diagnosed MM.

TERTIARY OBJECTIVES:

  1. PDL-1 expression on myeloma cells and non-tumor cell compartments from the bone marrow will be assessed at baseline.

II. Measures of T-cell activation / exhaustion will be assessed at baseline and after cycle 1, cycle 2, cycle 3, and cycle 4.

III. Natural killer (NK) cell function and numbers will be evaluated at baseline and after cycle 1, cycle 2, cycle 3, and cycle 4.

OUTLINE:

Patients receive lenalidomide orally (PO) daily on days 1-21 and dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.

After completion of study treatment, patients are followed up every 3 months or 6 months for up to 3 years.

Being tested
Dexamethasone, Laboratory Biomarker Analysis, Lenalidomide, Pembrolizumab
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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02880228
Study groupRoleWhat they receive
Treatment (lenalidomide, dexamethasone, pembrolizumab)ExperimentalPatients receive lenalidomide PO daily on days 1-21 and dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.
Receives: Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Biological: Pembrolizumab

What is being measured

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

  1. Proportion of Complete Response Plus Very Good Partial Response (VGPR)

    The International Myeloma Working Group response criteria was used to assess response to therapy. The proportion of VGPR response at any time during treatment with pembrolizumab added to lenalidomide and dexamethasone will be estimated by the number of patients achieving a VGPR, CR, or sCR at any time divided by the total number of evaluable patients. A very good partial response (VGPR) is defined as as a demonstration of:

    • Serum and urine M-component detectable by immunofixation but not on electrophoresis c or
    • greater than 90% reduction in serum m-component and urine m-component <100 mg/24 h
    • If the only measurable disease is FLC, a ≥90% reduction in the difference between involved and involved FLC levels

    The proportion of successes will be estimated by the number of patients demonstrating a VGPR or better divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

    Measured: Up to 112 days

Secondary outcomes (4)

  1. Progression-free Survival

    Progression-free survival is defined as the time from registration to the earliest date of documentation of disease progression or death due to any cause. Patients who receive subsequent treatment for myeloma before disease progression will be censored on the date of their last disease assessment prior to initiation of the subsequent treatment. Transplant will not be considered subsequent treatment. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

    Measured: From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years

  2. Partial Response (PR)

    The PR response after 4 cycles of induction treatment with pembrolizumab added to lenalidomide and dexamethasone will be estimated by the number of patients who achieve a PR, VGPR, CR, or sCR after 4 cycles divided by the total number of evaluable patients. A PR is defined by the following criteria:>

    • If present at baseline, ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein or to <200 mg/24hrs>
    • If the only measurable disease is FLC, a ≥50% reduction in the difference between involved and involved FLC levels>
    • If the only measurable disease is BM, a ≥50% reduction in BM PC's (provided the baseline PC's was ≥30%)>
    • If present at baseline, ≥50% reduction in the size of soft tissue plasmacytomas>

    Exact binomial 95% confidence intervals for the true success rate will be calculated.

    Measured: Up to 112 days

  3. Proportion of Successful Stem Cell Collection

    The proportion of successful stem cell collection following initial therapy with the combination of pembrolizumab, lenalidomide and dexamethasone in patients with newly diagnosed MM will be estimated by the number of patients with a successful stem cell collection divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true successful proportion will be calculated.

    Measured: Up to 112 days

  4. Survival Time

    Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Measured: From time of registration to death due to any cause, assessed up to 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 posted26 Aug 2016 (estimated)
  2. Study start16 Sep 2016
  3. Primary completion6 Jul 2017
  4. Study completion29 Jul 2018

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
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02880228
Sponsor's protocol ID
MC1588
Other IDs
NCI-2016-01290, MC1588, P30CA015083
Status last verified
Apr 2019
First submitted
18 Aug 2016
Last updated
30 Jul 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dexamethasone, Laboratory Biomarker Analysis and Lenalidomide in people with Plasma Cell Myeloma, run by Mayo Clinic at 2 sites 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 28 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 30 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 2 sites 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 17 Jul 2019). 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?

Proportion of Complete Response Plus Very Good Partial Response (VGPR) (time frame: Up to 112 days). 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 NCT02880228.

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 2019.

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