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Recurrent Plasma Cell MyelomaPhase 2NCT03506360

Pembrolizumab, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

A Phase 2 study testing Dexamethasone, Ixazomib Citrate and Laboratory Biomarker Analysis in people with Recurrent Plasma Cell Myeloma, run by Mayo Clinic at 1 site 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 works when given together with ixazomib citrate and dexamethasone in treating patients with multiple myeloma that has come back (relapsed). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Plasma Cell Myeloma
What is being tested?
Dexamethasone, Ixazomib Citrate and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
19 Jun 2018to 10 Dec 2020
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 of relapsed, symptomatic multiple myeloma by International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma
  • Age >= 18 years
  • Calculated creatinine clearance (using Cockcroft-Gault equation below) >= 30 mL/min (obtained =< 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration)
  • Platelet count >= 75000/mm^3; Note: Platelet transfusion is not allowed =< 3 days prior to registration (obtained =< 14 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)
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  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (obtained =< 14 days prior to registration)
  • Must have relapsed or refractory disease after treatments including three therapies: proteasome inhibitors, immunomodulatory imide drugs (IMiDs), and anti-CD38 antibody
  • 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 informed written consent
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Willing to follow strict birth control measures;
  • Female patients: If they are of childbearing potential, 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 120 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 bone marrow and blood samples for planned research

Who cannot join

  • Myeloma disease that is refractory to ixazomib treatment
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include early stage cancers (carcinoma in situ or stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
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  • 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 =< 14 days prior to study registration; 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
  • Has active autoimmune disease that has required systemic treatment =< 2 years prior to study registration (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
  • Has a known history of interstitial lung disease
  • Has an active infection requiring systemic therapy
  • Has a history of 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
  • Has 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
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has 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)
  • Has a known history of active TB (Bacillus tuberculosis)
  • Has received a live vaccine =< 30 days prior to study registration
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Allogeneic hematopoietic stem cell transplant
  • Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort =< 14 days prior to registration
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase 2 Trial of Pembrolizumab, Ixazomib, and Dexamethasone for Relapsed Multiple Myeloma

This phase II trial studies how well pembrolizumab works when given together with ixazomib citrate and dexamethasone in treating patients with multiple myeloma that has come back (relapsed). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ixazomib citrate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving pembrolizumab together with ixazomib citrate and dexamethasone may work better in treating patients with multiple myeloma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the overall response rate (>= partial response [PR]) of pembrolizumab in combination with standard doses of ixazomib citrate (ixazomib) and dexamethasone, in patients with relapsed symptomatic multiple myeloma (MM).

SECONDARY OBJECTIVES:

  1. To determine the >= very good partial response (VGPR) and complete response (CR) rate of pembrolizumab added to standard doses of ixazomib and dexamethasone in relapsed myeloma.

II. To determine the progression free survival and overall survival among patients with relapsed MM following treatment with the combination of pembrolizumab, ixazomib and dexamethasone.

III. To determine the toxicities associated with pembrolizumab added to standard doses of ixazomib and dexamethasone in patients with relapsed MM.

CORRELATIVE RESEARCH:

  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 and cycle 3.

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

OUTLINE:

Patients receive ixazomib citrate orally (PO) on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab intravenously (IV) over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months until progressive disease, and then every 6 months for up to 2 years.

Being tested
Dexamethasone, Ixazomib Citrate, Laboratory Biomarker Analysis, 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

  • Ixazomib CitrateDrug

    Also called MLN-9708, MLN9708, Ninlaro

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

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

    Given IV

Study groups in NCT03506360
Study groupRoleWhat they receive
Treatment (ixazomib citrate, pembrolizumab, dexamethasone)ExperimentalPatients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

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

  1. Overall Response Percentage

    Defined as a partial response or better noted as the objective status on two consecutive evaluations. The proportion of successes will be estimated by the number of successes 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 9 months

Secondary outcomes (5)

  1. >= Very Good Partial Response (VGPR) Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone

    Will be estimated by the number of patients who achieve a VGPR, complete response (CR), or stringent complete response (sCR) at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success rate will be calculated.

    Measured: Up to 9 months

  2. Complete Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone

    Will be estimated by the number of patients who achieve a CR or sCR at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success rate will be calculated.

    Measured: Up to 2 years

  3. Survival Time

    The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Measured: Up to 2 years

  4. Progression-free Survival

    The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

    Measured: Up to 2 years

  5. Incidence of Adverse Events

    Graded according National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

    Measured: Up to 9 months

Timeline

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

  1. First posted24 Apr 2018
  2. Study start19 Jun 2018
  3. Primary completion14 Nov 2019
  4. Study completion10 Dec 2020

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
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03506360
Sponsor's protocol ID
MC1782
Other IDs
NCI-2018-00590, MC1782, 17-008639
Status last verified
Jan 2024
First submitted
11 Apr 2018
Last updated
9 Jan 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dexamethasone, Ixazomib Citrate and Laboratory Biomarker Analysis in people with Recurrent Plasma Cell Myeloma, run by Mayo Clinic 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 26 inclusion and 29 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 9 Jan 2024. 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 14 Nov 2022). 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 Percentage (time frame: Up to 9 months). 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 NCT03506360.

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 9 Jan 2024.

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