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Multiple MyelomaPhase 2NCT05050305

Marizomib Central Nervous System (CNS)

A Phase 2 study testing Marizomib, Pomalidomide and Dexamethasone in people with Multiple Myeloma and Multiple Myeloma in Relapse, run by Dana-Farber Cancer Institute at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This research is being done to test whether the investigational drug marizomib is safe and effective when used in combination with standard of care drugs for the treatment of multiple myeloma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Marizomib, Pomalidomide and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
Mar 2024to Dec 2027
Phase
Phase 2
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

  • Previously diagnosed with MM based on standard IMWG criteria and currently requires treatment.
  • Patients in the CNS-involved cohort must have CNS involvement of MM as defined by meningeal myelomatosis and/or radiological evidence of leptomeningeal disease and/or intracranial plasmacytoma involving brain parenchyma.
  • Patients in the CNS-involved cohort must have received at least one or more previous lines of therapy including an IMiD and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.
  • Patients in the RRMM cohort must have received at least two or more previous therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.
  • Patients in the RRMM cohort must have measurable disease defined as at least one of the following:
  • Serum M protein ≥ 0.5 g/dL (≥5 g/L)
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  • Urine M protein ≥200 mg/24 hours
  • Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
  • Screening Laboratory evaluations within the following parameters
  • Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L) (Growth factors cannot be used within 14 days before first drug administration)
  • Platelet count ≥ 75,000 cells/dL (75 x 109/L) (without transfusions required during the 14 days prior to initiation of therapy)
  • Hemoglobin ≥ 8.0 g/dl (RBC transfusions are permitted)
  • Total Bilirubin ≤ 1.5 X upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN
  • Calculated creatinine clearance ≥ 45 mL/min
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
  • All study participants must be registered into the mandatory POMALYST REMS® program, and be willing and able to comply with the requirements of the POMALYST REMS® program.
  • Females of reproductive potential must adhere to the scheduled testing as required in the POMALYST REMS® program.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
  • Patients have given voluntary written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Prior exposure to marizomib. and primary refractoriness to pomalidomide or a pomalidomide combination. Prior pomalidomide exposure is permitted but patients must have shown tolerance (defined as no grade 3 or greater non-hematologic toxicity), as well as responsiveness to pomalidomide-based therapy (defined as MR or better).
  • Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy/watchful waiting.
  • Known GI disease or GI procedure that could interfere with the oral absorption of pomalidomide including difficulty swallowing.
  • Systemic treatment, within 14 days before the first dose of pomalidomide, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
  • Peripheral neuropathy ≥ Grade 3, or Grade 2 with pain on clinical examination during the screening period.
  • Any medical or psychiatric illness that in the investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study.
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  • Current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, Grade 3 thromboembolic event or myocardial infarction within the past 6 months.
  • The following therapies within the stated time frames prior to initiation of therapy: previous cytotoxic therapies, including cytotoxic investigational agents, for MM within 3 weeks; IMiDs, PIs, corticosteroids, other approved therapeutics and monoclonal antibodies (Mabs) within 2 weeks; and investigational therapies within 4 weeks. Please note consideration of the interval for investigational agents from already approved classes of drug in MM (e.g. Cell-Mods, Mabs) can be considered on a case by case basis with the PI. Prior peripheral stem cell transplant within 12 weeks and the use of live vaccines within 30 days.
  • Prior allogeneic stem cell transplantation with active graft-versus-host-disease (grade 2 or greater).
  • Prior major surgical procedure or radiation therapy within 4 weeks of initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy).
  • Daily requirement for corticosteroids equivalent to > 10 mg/day prednisone, except for inhalation corticosteroids, for the RRMM cohort. For patients with CNS involvement who require a higher dose of corticosteroids for control of vasogenic edema (e.g. 16 mg/day dexamethasone), eligibility will be determined on a case-by-case basis after discussion with the PI.
  • Any > Grade 1 adverse reaction unresolved from previous treatments according to the National Cancer Institute - Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTC AE v.5.0). The presence of alopecia any grade or peripheral neuropathy ≤ Grade 2 without pain is allowed.
  • Concurrent symptomatic amyloidosis or plasma cell leukemia.
  • POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).
  • Known active infection requiring parenteral or oral anti-infective treatment within 7 days of start of therapy.
  • Known human immunodeficiency virus or active hepatitis C viral infection.
  • Active hepatitis B viral infection (defined as HBsAg+).
  • Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-).
  • Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may be enrolled at the discretion of the investigator after consideration of risk of reactivation.
  • Pregnant or breast-feeding females.
  • Participants who are receiving any other investigational agents.
  • History of erythema multiforme or severe hypersensitivity to prior IMiD's®.
  • Inability to tolerate thromboprophylaxis.
  • 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.
  • Known hypersensitivity to thalidomide or lenalidomide or other drugs included in this study.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, pomalidomide or similar drugs.
  • -

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase 2 Study With Safety Run-In of Marizomib, Pomalidomide, and Dexamethasone For Relapsed and Refractory Multiple Myeloma and CNS Myeloma

This research is being done to test whether the investigational drug marizomib is safe and effective when used in combination with standard of care drugs for the treatment of multiple myeloma.

Read the detailed description

This is a Phase 2 single-arm study, incorporating two cohorts and using the combination of marizomib plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma (RRMM) patients and in RRMM patients with CNS involvement.

This research study involves a three drug chemotherapy regimen which includes taking the study drug marizomib, as well as pomalidomide and dexamethasone. The U.S. Food and Drug Administration (FDA) has not approved marizomib as a treatment for any disease. The U.S. Food and Drug Administration (FDA) has approved pomalidomide and dexamethasone as a treatment option for multiple myeloma.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. As the study is looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have multiple myeloma, not everyone who participates in this research study will receive the same dose of the study drug. The dose received will depend on the number of participants who have been previously enrolled in the study and how well participants have tolerated their doses. Participants will receive study treatment for as long as participants do not have serious side effects and their disease does not get worse.

It is expected that about 48 people will take part in this research study.

Bristol-Myers Squibb is supporting this research study by providing funding and study drug.

Being tested
Marizomib, Pomalidomide, Dexamethasone
Keywords
Multiple Myeloma, Multiple Myeloma in Relapse, Multiple Myeloma, Refractory, CNS Myeloma
Medical subject headings
Multiple Myeloma

What participants receive

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

  • MarizomibDrug

    Also called Salinosporamide A

    Intravenous Infusion

  • PomalidomideDrug

    Also called Pomalyst

    Taken orally

  • DexamethasoneDrug

    Also called Decadron, Dexasone, Hexadrol, Maxidex

    Taken orally

Study groups in NCT05050305
Study groupRoleWhat they receive
Marizomib plus pomalidomide and dexamethasoneExperimentalA safety run-in using a modified 3+3 dose de-escalation design with relapsed/refractory multiple myeloma (RRMM) cohort, expanded to a total of 16 participants once recommended phase 2 does (RP2D) has been identified. * Marizomib (MRZ) at a pre-determined dose on Days 1, 8, 15, 22 of a 28 day study cycle * Pomalidomide (POM) at a daily predetermined dose on Days 1-21 of a 28 day study cycle * Dexamethasone (DEX) at a daily predetermined dose on Days 1, 2, 8, 9, 15, 16, 22, 23 of a 28 day study cycle Simultaneously, relapsed/refractory multiple myeloma (RRMM) with central nervous system (CNS) involvement cohort will receive an identical modified 3+3 dose de-escalation design and expanded to an efficacy-evaluable total of 30 patients once recommended phase 2 does (RP2D has been identified
Receives: Drug: Marizomib; Drug: Pomalidomide; Drug: Dexamethasone

What is being measured

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

  1. Maximum Tolerated Dose (MTD) Safety Run-In

    MTD is defined as the highest dose level where no patients (of the 6 treated) develop a dose limiting toxicity (DLT)

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, up to 5 years

  2. Dose Limiting Toxicity (DLT)

    Toxicity summaries will be stratified by dose level, grade, and treatment attribution

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, up to 5 years

  3. The number and proportion of adverse events, graded as defined by CTCAE version 5.0.

    CTCAE version 5.0.

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, up to 5 years

  4. Overall response rate (ORR)

    Assessed using the updated International Myeloma Working Group Response Criteria (IMWG) (Rajkumar 2011).

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, up to 5 years

Secondary outcomes (4)

  1. Time to response (TTR)

    Assessed using the updated International Myeloma Working Group Response Criteria (IMWG) (Rajkumar 2011).

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, up to 5 years

  2. Progression free survival (PFS)

    Assessed using the updated International Myeloma Working Group Response Criteria

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first. up to 5 years

  3. Duration of response (DOR)

    Assessed using the updated International Myeloma Working Group Response Criteria (IMWG) (Rajkumar 2011).

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, up to 5 years

  4. Overall survival (OS)

    Assessed using the updated International Myeloma Working Group Response Criteria

    Measured: From date of enrollment until date of death from any cause, up to 5 years

Timeline

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

  1. First posted20 Sep 2021
  2. Study startMar 2024 (estimated)
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2027 (estimated)

Why it stopped: Study support withdrawn

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05050305
Sponsor's protocol ID
20-551
Status last verified
Jul 2024
First submitted
14 Apr 2021
Last updated
16 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Marizomib, Pomalidomide and Dexamethasone in people with Multiple Myeloma and Multiple Myeloma in Relapse, run by Dana-Farber Cancer Institute 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 21 inclusion and 27 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 16 Jul 2024. 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?

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?

Maximum Tolerated Dose (MTD) Safety Run-In (time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, up to 5 years). The study lists 4 primary outcomes in all. 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 NCT05050305.

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 16 Jul 2024.

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