A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HPN217 in Patients with Relaped/Refractory Multiple Myeloma

Overview

About this study

The purpose of this study is to evaluate HPN217 as monotherapy to assess the safety, tolerability and pharmacokinetics 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:

  • Able to read, understand and provide written informed consent.
  • Patients ≥ 18 years of age at the time of signing informed consent.
  • Documented RRMM for which no standard therapy options are anticipated to result in a durable remission. Relapse defined as progressive disease after initial response (minimal response [MR] or better) to previous treatment, more than 60 days after cessation of last treatment. Refractory disease defined as < 25% reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment.
  • Received at least 3 prior therapies (including proteasome inhibitor, immune modulatory drug, and an anti-CD38 antibody; patients should not be a candidate for or be intolerant of all established therapies known to provide clinical benefit in multiple myeloma).
  • Measurable disease defined as at least one of the following:
    • Serum M-protein ≥ 0.5 g/dL;
    • Urine M-protein ≥ 200 mg/24 hours;
    • Serum free light chain (FLC) assay: Involved FLC level ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal serum FLC ratio (1.65)
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Adequate hematologic status, including:
    • Absolute neutrophil count (ANC) ≥ 1000 cells/μL;
    • Platelet count ≥ 50,000/μL (without transfusions);
    • Hemoglobin ≥ 8 g/dL.
    • Note: To meet all above hematological criteria, transfusions and supportive therapy (e.g., granulocyte colony stimulating factors) may be administered prior to Screening. However, in all such instances, levels of the relevant parameters (for which the patient was transfused) must be allowed to stabilize for at least 72 hours after dosing/infusion, after which Screening labs may be redrawn.
  • Adequate renal function, including:
    • Calculated creatinine clearance ≥ 30 mL/min using the formula of Cockcroft and Gault.
  • Adequate hepatic function, including:
    • Total bilirubin ≤ 1.5 × upper limit of normal (ULN), regardless of direct bilirubin;
    • AST and ALT ≤ 3.0 × ULN (≤ 5.0× ULN if due to myeloma involvement);
    • Alkaline phosphatase ≤ 3× ULN (≤ 5.0× ULN if due to myeloma involvement).
  • Serum calcium (corrected for albumin) at or below the ULN range; patient may enroll with hypercalcemia at Screening if hypercalcemia resolves with standard treatment by Cycle 1 Day 1, prior to study therapy initiation.
  • Resolved acute effects of any prior therapy to baseline severity or CTCAE version 5.0 Grade ≤1.
  • Willing to complete all scheduled visits and assessments at the institution administering therapy.

Exclusion Criteria:

  • Plasma cell leukemia; non-secretory myeloma (e.g., solitary plasmacytoma).
  • Patients with only extramedullary relapse of multiple myeloma who do not meet inclusion for measurable disease.
  • Note: All patients with extramedullary disease and measurable disease but must have a radiological scan (e.g., CT/PET) to establish a baseline for their extramedullary disease at Screening (unless scans taken within the 2 weeks preceding Screening are available and adequate for assessment of extramedullary disease at baseline).
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes).
  • Waldenstrom’s macroglobulinemia.
  • Localized radiation therapy to disease site(s) within 2 weeks of treatment.
  • Prior autologous peripheral stem cell transplant or prior autologous bone marrow transplantation within < 90 days of the start of study.
  • Prior allogeneic stem cell transplantation or solid organ transplantation within 12 months of Screening. However, any patient receiving immunosuppressive medication will be excluded.
  • Prior corticosteroid use within < 2 weeks of treatment, with the exception of topical or temporary use (≤ 20 mg/day for no more than 5 days total), which may be allowed after approval by the CRO Medical Monitor.
  • Known central nervous system involvement by multiple myeloma.
  • Untreated spinal cord compression.
  • Concurrent treatment with anti-TNFα therapies, or other immune suppressive drugs within the 2 weeks prior to Screening.
  • History of clinically significant cardiovascular disease, unstable angina pectoris, recent myocardial infarction, congestive heart failure, uncontrolled cardiac arrhythmia, history of cerebral vascular accident, transient ischemic attack, or other co-morbid condition that in the opinion of the investigator would compromise the patient’s safety or interfere with the evaluation of the safety of HPN217. Participants with cardiovascular disease that is stable for at least 6 months while on treatment may be enrolled after documenting evaluation and approval of trial participation by a cardiologist.
  • Known congestive heart failure (New York Heart Association Class 3).
  • History of any thromboembolic event within 3 months prior to first dose of HPN217.
  • Active infectious disease requiring treatment within 2 weeks of Screening.
  • Active or chronic hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
  • Clinically active or chronic liver disease, including liver cirrhosis of Child-Pugh class C
  • Other malignancy within 3 years of Screening (except basal cell or squamous cell carcinoma of the skin or carcinoma in situ treated with curative therapy).
  • Last anticancer treatment within 2 weeks of scheduled dosing (or 5 half-lives of drug, whichever is shorter).
  • Major surgery within 4 weeks of scheduled dosing.
  • Pulmonary, hematologic, renal, hepatic, gastrointestinal, neurological or psychiatric disease that would limit compliance with study requirements.
  • Any serious underlying medical or psychiatric condition (e.g., alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the patient to understand informed consent or that in the opinion of the Investigator would contraindicate the patient’s participation in the study or confound the results of the study.
  • Known hypersensitivity, allergies, or intolerance to immunoglobulins, or to any excipient contained in HPN217 (see Investigator’s Brochure).
  • Treatment with another investigational drug within 4 weeks before start of study treatment or concomitantly with this study.
  • Patient has unresolved AEs ≥ Grade 2 (National Cancer Institute [NCI] CTCAE version 5.0) except for:
    • Alopecia;
    • Known peripheral neuropathy (peripheral neuropathy ≥ Grade 3 will be excluded);
    • Patient with irreversible toxicity not reasonably expected to be exacerbated by any of the investigational products may be included (e.g., hearing loss) after consultation with the Medical Monitor.
    • Pregnant or breast-feeding.
    • Women of childbearing potential not using a highly effective method of birth control during the study until 6 months after the last dose of HPN217. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e., < 1% per year) when used consistently and correctly (including implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or vasectomized partner; barrier methods of contraception are accepted if condom or occlusive cap is used together with spermicides [e.g., foam, gel]) and a highly effective method of birth control. Female patients will be considered of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or postmenopausal (12 months with no menses without an alternative medical cause).
    • Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the study and for a minimum of 6 months after treatment.

Eligibility last updated 9/30/21. 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

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-20507823

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