A Study to Evaluate ION251 to Treat Patients with Relapsed/Refractory Multiple Myleoma

Overview

About this study

The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION251 in patients with relapsed/refractory multiple myeloma.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
  • Age ≥ 18 years at the time of informed consent.
  • Satisfy the following:
    • Females: must be non-pregnant and non-lactating and either:
      • surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy);
      • post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved)
      • abstinent*; or
      • if engaged in sexual relations and of child-bearing potential, agree to use highly effective contraceptive methods from the time of signing the informed consent form until at least 13 weeks after the last dose of Study Drug (ION251).
    • Males: Surgically sterile or if engaged in sexual relations with a female of child-bearing potential, either the patient or their female partner is utilizing a highly effective contraceptive method from the time of signing the informed consent form until at least 13 weeks after the last dose of Study Drug (ION251).

* Abstinence is only acceptable as true abstinence; i.e., when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception.

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Measurable multiple myeloma (MM) et al. defined as at least one of the following: serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours or serum free light chain level ≥ 10 mg/dL (provided the serum free light chain ratio was abnormal).
  • In need of systemic treatment for MM and either is refractory to or has failed treatment with, is intolerant to or has refused, or is not otherwise a candidate in the opinion of the Investigator, for any of the currently available established therapies known to provide clinical benefit in relapsed/refractory MM.  Refractory to treatment is defined as documented MM disease progression while on or within 60 days from the last dose of treatment (Rajkumar et al. 2011).
  • Has an estimated life expectancy of at least 12 weeks.
  • Have recovered from all toxicities of prior therapy to ≤ Grade 1 (or baseline) by Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 (exceptions: peripheral neuropathy ≤ Grade 2 and any toxicities that in the view of the Investigator is not a clinically significant (CS) safety risk for further therapy administration, such as but not limited to: alopecia, fatigue, erectile dysfunction, hot flashes, cough, and urinary incontinence).
  • Termination from prior line of multiple myeloma therapy at least 14 days before first administration of ION251 (i.e., Cycle 1 Day 1).

Exclusion Criteria:

  • Clinically significant abnormalities in medical history (e.g., acute coronary syndrome within 6 months of Screen, major surgery within 3 months of Screen) or physical examination.
  • Screen laboratory results as follows, or any other clinically significant abnormalities in screen laboratory values that would render a patient unsuitable for inclusion:
    • ALT or AST > 2 × ULN;
    • Total bilirubin > 1.3 × ULN (patients with Gilbert’s Syndrome may be eligible if direct bilirubin < 1 × ULN and results reviewed with the Medical Monitor);
    • Absolute neutrophil count ≤ 1.0 k/mm^3;
    • Platelet count < 50 k/mm^3;
    • Hemoglobin < 8.0 g/dL;
    • Estimated glomerular filtration rate (eGFR, by CKD-EPI equation < 50 mL/min/1.73 m^2 );
    • Urine albumin creatinine ratio > 100 mg/g.
  • Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1.
  • Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
  • Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B. Antibody positivity for HCV is allowed if patient is below detection limit for plasma or serum HCV RNA, is not currently receiving antiHCV therapy, and has not received such therapy for > 6 months.
  • History of or current plasma cell leukemia defined as > 2.0 × 10^9 /L circulating plasma cells by standard differential, clinically significant light chain amyloidosis, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone or extramedullary plasmacytoma as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm.
  • History of atypical hemolytic uremic syndrome.
  • Blood or platelet transfusion during the 6 days prior to Screen.
  • Treated or untreated parenchymal brain metastases or leptomeningeal disease. Current active malignant epidural disease is also excluded. Previously treated epidural disease does not exclude the patient from study as long as disease is inactive.
    • Note: CT or magnetic resonance imaging (MRI) of brain is not needed to rule these out unless the patient has clinical symptoms suggestive of CNS metastases.
  • Uncontrolled hypertension (systolic pressure ≥ 160 mm Hg and/or diastolic pressure ≥ 100 mm Hg).
  • Presence or history of malignancies other than multiple myeloma, except non-melanoma skin cancers or carcinoma in situ of the cervix that has been successfully treated. Patients with a history of other malignancies that have been treated with curative intent and which have no recurrence within 3 years may also be eligible.
  • Treatment with another investigational drug, biological agent, or device within 14 days before first administration of ION251 (i.e., Cycle 1 Day 1).
  • Previous treatment with an oligonucleotide (including small interfering ribonucleic acid [siRNA]) within 4 months of Screen if single dose received, or within 12 months of Screening if multiple doses received.
  • Presence of a bleeding disorder or an underlying disease state associated with active bleeding.
  • Recent history of, or current drug or alcohol abuse.
  • QTc interval > 470 msec during Screen.
  • Concurrent treatment with anti-myeloma drugs or biologicals (exception: ongoing treatment with bisphosphonates and RANK-ligand inhibitors is allowed provided dose regimen has been stable for the ≥ 4 weeks before first administration of ION251).
  • Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the patient unsuitable for inclusion, or could interfere with the subject participating in or completing the Study.

Eligibility last updated 8/31/21. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Morie Gertz, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Sikander Ailawadhi, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Peter Bergsagel, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20505899

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