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Refractory Multiple MyelomaPhase 1NCT04355039

INCB053914 and Pomalidomide With Dexamethasone for Relapsed and/or Refractory Multiple Myeloma

A Phase 1 study testing Pomalidomide, Dexamethasone and INCB053914 50 mg bis in die (BID) in people with Refractory Multiple Myeloma and Relapse Multiple Myeloma, run by Medical College of Wisconsin.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a prospective, single-center, open-label phase Ib study aimed at determining a recommended phase II dose of INCB053914 and pomalidomide with dexamethasone. The trial will follow a 3 + 3 phase I dose-escalation design. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pomalidomide, Dexamethasone and INCB053914 50 mg bis in die (BID)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
1 Jul 2021to 1 Jul 2024
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

  • Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Patient should have received ≥2 lines of therapy including at least two consecutive cycles of lenalidomide and a proteasome inhibitor alone or in combination and should be relapsed and/or refractory to lenalidomide and a proteasome inhibitor.
  • Measurable disease as defined (at least one of the following):
  • Serum M-protein level ≥0.5 g/dl or urine M-protein level ≥200 mg/24 hours. OR
  • Light chain multiple myeloma without measurable disease in the urine: serum Ig free light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio.
  • Non-secretory multiple myeloma (MM) with bidimensionally measurable plasmacytoma.
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  • Male or female subjects ≥18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Female subjects must meet one of the following:
  • Postmenopausal for at least one year before enrollment, OR
  • Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), OR
  • If subject is of childbearing potential (defined as not satisfying either of the above two criteria), agrees to practice two acceptable methods of contraception (combination methods require use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 21days after the last dose of study agent, OR o Agrees 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, postovulation methods] and withdrawal are not acceptable contraception methods.)
  • Male subjects, even if surgically sterilized (i.e., status postvasectomy), must agree to one of the following:
  • Practice effective barrier contraception during the entire study period and through 90 calendar days after the last dose of study agent, OR
  • o Agrees 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.)

Who cannot join

  • Prior use of PIM kinase inhibitors.
  • Prior pomalidomide refractory patients (last prior therapy was pomalidomide-containing regimen and/or patients within three months of pomalidomide dose).
  • Diagnosed or treated for malignancy other than multiple myeloma, except:
  • Malignancy treated with curative intent and with no known active disease present for ≥2 years before enrollment.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ (e.g., cervical, breast) with no evidence of disease.
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  • Exhibiting clinical signs of meningeal or central nervous system involvement by multiple myeloma.
  • Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C.
  • Concurrent medical condition or disease (e.g., active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study. Specifically, any potential subject who is unsuitable for autologous stem cell transplant (ASCT) would be excluded from the study.
  • Clinically significant cardiac disease, including:
  • Myocardial infarction within six months before Cycle 1, Day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
  • Uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] Version 5 grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
  • Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec.
  • Any of the following laboratory test results during the screening phase:
  • Absolute neutrophil count <1.0 × 109/L; no granulocyte-colony stimulating factor (G-CSF) treatment in the past seven days are allowed.
  • Hemoglobin level ≤7.5 g/dL (≤5 mmol/L); blood transfusions to maintain hemoglobin >7.5 g/dL are acceptable.
  • Platelet count <50 × 109/L for subjects in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count <50 × 109/L; no platelet transfusions in the past seven days are allowed.

About this study

Official title: A Phase I Study of INCB053914 (Pan-PIM Kinase Inhibitor) and Pomalidomide With Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

This is a prospective, single-center, open-label phase Ib study aimed at determining a recommended phase II dose of INCB053914 and pomalidomide with dexamethasone. The trial will follow a 3 + 3 phase I dose-escalation design.

Read the detailed description

This is a prospective, single-center phase I clinical study aimed at determining the maximum-tolerated dose and safety of INCB053914 (pan-PIM kinase inhibitor) and pomalidomide with dexamethasone in patients with relapsed and/or refractory multiple myeloma. Three candidate dose levels of INCB053914, 50 mg, 65 mg, and 80 mg twice daily will be considered.

The research team will utilize a 3+3 design to determine a safe dose of INCB053914 combined with fixed doses of pomalidomide (4 mg Days 1- Days 21) and dexamethasone (40 mg Days 1, 8, 15, 22).

The first three patients will be treated with INCB053914 twice daily at a dose of 50 mg.

Dose-limiting toxicity (DLT) assessment during the first 28-day cycle will be the basis for maximum-tolerated dose assessment.

Being tested
Pomalidomide, Dexamethasone, INCB053914 50 mg bis in die (BID), INCB053914 65 mg BID, INCB053914 80 mg BID
Keywords
Multiple Myeloma, Refractory Multiple Myeloma, Relapse Multiple Myeloma, INCB053914, pan-PIM Kinase Inhibitor
Medical subject headings
Multiple Myeloma

What participants receive

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

  • PomalidomideDrug

    Also called Pomalyst

    4 mg Days 1-21

  • DexamethasoneDrug

    Also called Ozurdex

    40 mg Days 1, 8, 15 and 22

  • INCB053914 50 mg bis in die (BID)Drug

    Also called pan-PIM Kinase Inhibitor

    Dose level 0: 50 mg BID

  • INCB053914 65 mg BIDDrug

    Also called pan-PIM Kinase Inhibitor

    Dose level 1: 65 mg BID

  • INCB053914 80 mg BIDDrug

    Also called pan-PIM Kinase Inhibitor

    Dose level 2: 80 mg BID

Study groups in NCT04355039
Study groupRoleWhat they receive
Pomalidomide, Dexamethasone & INCB053914 50 mg twice dailyExperimentalINCB053914 will have a dose escalation in a 3 + 3 design.
Receives: Drug: Pomalidomide; Drug: Dexamethasone; Drug: INCB053914 50 mg bis in die (BID)
Pomalidomide, Dexamethasone & INCB053914 65 mg twice dailyExperimentalINCB053914 will have a dose escalation in a 3 + 3 design.
Receives: Drug: Pomalidomide; Drug: Dexamethasone; Drug: INCB053914 65 mg BID
Pomalidomide, Dexamethasone & INCB053914 80 mg twice dailyExperimentalINCB053914 will have a dose escalation in a 3 + 3 design.
Receives: Drug: Pomalidomide; Drug: Dexamethasone; Drug: INCB053914 80 mg BID

What is being measured

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

  1. The number of subjects with dose-limiting toxicities.

    The safety of INCB053914 with pomalidomide and dexamethasone in participants with relapsed and/or refractory multiple myeloma.

    Measured: 28 days

Secondary outcomes (8)

  1. The recommended phase II dose of INCB053914.

    Based on number of dose-limiting toxicities.

    Measured: 28 days

  2. Progression-free survival.

    This measure is the number of months participants remain free from evidence of disease. This will be captured using International Myeloma Working Group criteria.

    Measured: 2 Years

  3. Overall survival.

    Overall survival is defined from the number of months from initiation of treatment until death due to any cause. Participants without an observed progression / death event will be censored at the last follow-up or end of study.

    Measured: 2 Years

  4. Duration of response.

    The number of months from the date of first documented response (complete or partial) to the time of the next relapse/progression. This will be captured using International Myeloma Working Group criteria.

    Measured: 2 Years

  5. Efficacy of bone protective effect of INCB053914 in combination with pomalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma.

    The number of subjects with negative serum C terminal telopeptide type-X (CTX). This is determined by a blood draw.

    Measured: 7 months

  6. The bone protective effect of INCB053914 in combination with pomalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma.

    The number of subjects with positive serum N terminal propeptide of procollagen (P1NP). This is determined by a blood draw.

    Measured: 7 months

  7. The number of subjects with reduction of osteolytic lesions.

    This will be determined by positron emission tomography (PET) /MRI scans, using RECIST.

    Measured: 7 months

  8. The number of subjects with reduction of sclerosis formation.

    This will be determined by positron emission tomography (PET) /MRI scans, using RECIST.

    Measured: 7 months

Timeline

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

  1. First posted21 Apr 2020
  2. Study start1 Jul 2021 (estimated)
  3. Primary completion1 Jul 2023 (estimated)
  4. Study completion1 Jul 2024 (estimated)

Why it stopped: Terminated for lack of funding.

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04355039
Sponsor's protocol ID
IIT-Dhakal-INCB053914
Status last verified
Aug 2020
First submitted
17 Apr 2020
Last updated
19 Aug 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pomalidomide, Dexamethasone and INCB053914 50 mg bis in die (BID) in people with Refractory Multiple Myeloma and Relapse Multiple Myeloma, run by Medical College of Wisconsin.

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 15 inclusion and 17 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: withdrawn, as of the sponsor's last update on 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

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 was withdrawn before enrolling participants, so there are no results.

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?

The number of subjects with dose-limiting toxicities. (time frame: 28 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 NCT04355039.

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 19 Aug 2020.

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