Main info

Identificatie:

HOVON 178 WM

Sponsor:

HOVON

Working group party:

Lymphoma

Age:

>= 18

Stadium:

2de lijn

Echelon:

Level D

Active sites:

0

(of 7)

7 sites are pending

Title:

HOVON 178 R/R WM Epco study: A prospective phase I/II trial of epcoritamab in patients with relapsed or refractory Waldenstrom’s macroglobulinemia

Timeline

News

Flow

Details

Phase:

Prospective Phase I/II study

Monitoring Type:

HOVON Monitoring Visit

Objectives:

Phase Ib
Primary objective

• To establish the recommended phase II dose (RP2D) for epcoritamab in patients with R/R WM

Secondary objective

• To evaluate safety and tolerability of epcoritamab treatment in patients with R/R WM

Phase II
Primary objective

• To evaluate the preliminary efficacy of epcoritamab after 12 cycles in R/R WM patients in terms of major response rate (defined as complete remisson (CR), very good partial response (VGPR) or partial response (PR))

Secondary objectives

• To evaluate the efficacy of epcoritamab in terms of overall response rate (ORR) and categorical responses (PD, SD, MR, PR, VGPR, CR)including best response on protocol, categorical responses after 12 cycles and 24 cycles.
• To evaluate the efficacy of epcoritamab in terms of progression free survival (PFS), overall survival (OS), and treatment-free survival (TFS)
• To evaluate the efficicacy of epcoritamab in terms of time to next treatment (TTNT), time on treatment(TOT), time to response, time to best response and duration of response (DOR)
• To evaluate the quality of life (QoL)
• To evaluate the safety and tolerability
• To evaluate the incidence, severity, and type of infections

Eligibility

Inclusion Criteria:

• Diagnosed with WM, according to criteria in appendix A
• Age ≥ 18 years
• Indication for therapy based on IWMM consensus criteria
• Relapsed or refractory WM
• At least 1 prior line of systemic therapy for WM (including at least: either a BTK-inhibitor or an anti-CD20 antibody combined with chemotherapy)

*Measurable disease (IgM M-protein > 5 g/L or, in case M-protein is present but unquantifiable, total serum IgM level > 10 g/L)

• BM LPL infiltrate positive for CD20 at screening
• Acceptable Complete Blood Count (CBC), renal function, liver function and coagulation status, defined as per the following laboratory measurements:
  • Hemoglobin (Hb) > 5.6 mmol/L or Hb > 9 g/dL (unless related to WM)
  • Estimated creatinin clearance > 45 mL/min (Cockroft-Gault)
  • Serum ALT ≤ 3.0  upper limit of normal (ULN)
  • Serum AST ≤ 3.0  ULN
  • Total billirubin ≤ 1.5 x ULN (unless attributable to Gilbert’s syndrome or controlled autoimmune hemolytic anemia)
  • Absolute neutrophil count (ANC) > 1.0 x 109/L, unless neutropenia is due to BM involvement of WM in which case the minimum is > 0.5 x 109/L
  • Platelet count > 30 x109/L unless trombopenia is due to BM involvement of WM in which case the minimum is > 10 x 109/L
  • Prothrombin Time (PT), International Normalized Ratio (INR), and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN (unless receiving anticoagulation)
• ECOG/WHO performance status ≤ 2 (see appendix D)
• Negative serological testing for hepatitis B virus (HBV) (Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and hepatitis C virus (hepatitis C antibody). Patients who are positive for anti-HBc or hepatitis C antibody may be included if

they have a negative PCR within 6 weeks before enrollment. Those who are PCR positive will be excluded.
Please note: For patients positive for anti-HBc or antibodies for hepatitis C at screening but negative with PCR retesting, HBV-DNA or HCV-DNA PCR, respectively, has to be repeated at least every month until 12 months after the last dose of study treatment; For patients with
positive hepatitis B serology but negative HBV-DNA PCR, please refer to 9.1.3 for prophylactic use of lamuvidine.

• Negative pregnancy test at study entry for women of childbearing potential
• Agreement to use adequate contraception during the trial and for 4 months after last epcoritamab administration, for women of childbearing potential or men sexually active with a woman of childbearing potential

*Patient is capable of giving informed consent

• Written informed consent

Exclusion Criteria:

• Large cell transformation, central nervous system (CNS) involvement/Bing Neel Syndrome and/or AL (Amyloid Light-Chain) Amyloidosis
• Peripheral neuropathy of CTCAE grade ≥ 3
• Recent WM treatment:
  • For chemotherapy and/or rituximab and/or bortezomib and/or other proteasome inhibitors: within 4 weeks prior to first epcoritamab dose.
  • For BTK-inhibitors (monotherapy): within 14 days, prior to the first dose of epcoritamab
  • For autoSCT (autologous stem cell transplantation): 100 days prior to first epcoritimab dose.
  • For any other treatment and/or investigational drug: 4 weeks or 5 half-lives prior to first epcoritamab dose, whichever is longer, prior to the planned first dose of epcoritamab
• Prior solid organ or allogeneic hematopoietic stem cell transplantation (prior autoSCT is acceptable)
• Prior treatment with a CD3 × CD20 bispecific antibody
• Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy, including indication for systemic cortisteroids at > 10 mg daily prednisone or equivalent.
• History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components);
• Active bleeding or uncontrolled severe bleeding diathesis (e.g., hemophilia or severe von Willebrand disease);
• Ongoing active bacterial, viral, fungal, mycobacterial, parasitic or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrollment or within the previous 2 weeks prior to the planned first dose of trial drug, including COVID-19 infection.

Note that a past COVID-19 infection may be a risk factor, but if resolved and the subject is vaccinated, it may be allowable to enroll the subject.

• Has suspected active or inadequately treated latent tuberculosis;
• Severe cardiovascular disease (New York Heart Association (NYHA) classification III-IV) (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease);
• Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix FE);
• Severe neurological dysfunction including psychiatric disease CTCAE grade III-IV
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
• History of active malignancy (other than inclusion diagnosis) with the exception of:
  • Non-invasive basal cell or squamous cell skin carcinoma
  • Cervical carcinoma, stage 1B or less
  • Non-invasive, superficial bladder cancer
  • Prostate cancer with a current PSA level < 0.1 ng/mL
  • Any curable cancer with a CR of > 2 years duration
• Uncontrolled HIV infection. Patients with HIV positivity but with viral suppression (VL< lower limit of detection) and CD4 count > 350 for over 1 year, no history of AIDS-defining illnesses with the exception of lymphoma diagnosis may be enrolled.
• Patients with an active HBV and/or HCV infection.
• Patients with symptomatic IgG or IgA or non-secreting LPL
• Uncontrolled hyperviscosity syndrome and/or Plasmapheresis < 35 days prior to screening and/or initiation of study drug.
• Vaccination with live attenuated vaccines within 28 days prior to registration
• Major surgery within 28 days prior to registration
• Breastfeeding or pregnant female patients
• Current participation in another clinical trial with medicinal products
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals