Clinical Trials /

A Phase I/II Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma

NCT01796171

Description:

This study is a phase I/II, open-label study in patients with relapsed indolent non-Hodgkin lymphoma. Part A of the study included a phase I dose escalation to define the maximum tolerated / recommended dose for expansion of (177Lu)-lilotomab (Betalutin), and a phase IIa part to evaluate safety and preliminary efficacy. Part B of the study will assess the efficacy and safety of two different Betalutin/lilotomab dosing regimens in adult patients with relapsed rituximab / anti-CD20-refractory follicular lymphoma who have received 2 or more prior therapies.

Related Conditions:
  • Breast Invasive Ductal Carcinoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase I/II Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma
  • Official Title: A Phase I/II Study of Lutetium (177Lu)-Lilotomab Satetraxetan (Betalutin®) Antibody-radionuclide-conjugate for Treatment of Relapsed Non-Hodgkin Lymphoma.

Clinical Trial IDs

  • ORG STUDY ID: EudraCT: 2011-000033-36
  • NCT ID: NCT01796171

Conditions

  • Non-Hodgkin Lymphoma
  • Follicular Lymphoma

Interventions

DrugSynonymsArms
BetalutinPart A, Arm 1: with lilotomab pre-dosing
BetalutinPart A, Arm 2: without pre-dosing
BetalutinPart A, Arm 3: with rituximab pre-dosing
BetalutinPart A, Arm 4: with higher dose lilotomab pre-dosing
BetalutinPart A, Arm 5: with intermediate dose lilotomab pre-dosing
BetalutinPart B

Purpose

This study is a phase I/II, open-label study in patients with relapsed indolent non-Hodgkin lymphoma. Part A of the study included a phase I dose escalation to define the maximum tolerated / recommended dose for expansion of (177Lu)-lilotomab (Betalutin), and a phase IIa part to evaluate safety and preliminary efficacy. Part B of the study will assess the efficacy and safety of two different Betalutin/lilotomab dosing regimens in adult patients with relapsed rituximab / anti-CD20-refractory follicular lymphoma who have received 2 or more prior therapies.

Trial Arms

NameTypeDescriptionInterventions
Part A, Arm 1: with lilotomab pre-dosingExperimentalBetalutin, 10 MBq/kg b.w. in escalated doses with lilotomab pre-dosing.
  • Betalutin
Part A, Arm 2: without pre-dosingExperimentalBetalutin, 15 MBq/kg b.w. in escalated doses without pre-dosing.
  • Betalutin
Part A, Arm 3: with rituximab pre-dosingExperimentalBetalutin, 15 MBq/kg b.w. in escalated doses with rituximab pre-dosing.
  • Betalutin
Part A, Arm 4: with higher dose lilotomab pre-dosingExperimentalBetalutin, 15 MBq/kg b.w. in escalated doses with a higher dose lilotomab pre-dosing regimen.
  • Betalutin
Part A, Arm 5: with intermediate dose lilotomab pre-dosingExperimentalBetalutin, 20 MBq/kg b.w. with an intermediate dose lilotomab pre-dosing regimen.
  • Betalutin
Part BExperimentalBetalutin, 15 MBq/kg b.w. with 40mg lilotomab compared to Betalutin, 20 MBq/kg b.w. with 100mg/m2 lilotomab
  • Betalutin

Eligibility Criteria

        Part A:

        Inclusion Criteria:

          -  Histologically confirmed (by WHO classification) relapsed incurable non-Hodgkin B-cell
             lymphoma of following subtypes; follicular grade I-IIIA, marginal zone, small
             lymphocytic, lymphoplasmacytic, mantle cell.

          -  Age ≥ 18 years

          -  A pre-study WHO performance status of 0-1

          -  Life expectancy should be ≥ 3 months

          -  <25% tumour cells in bone marrow biopsy

          -  Measurable disease by radiological methods

        Exclusion Criteria:

          -  Absolute Neutrophil Counts (ANC) ≤ 1.5 x 109 /l

          -  Platelet count ≤ 150 x 109 /l

          -  Total bilirubin ≥ 30 mmol/l

          -  ALP and ALAT ≥ 4x normal level

          -  Creatinine ≥ 115 µmol/l (men), 97 µmol/l (women))

          -  Known CNS involvement of lymphoma

          -  Previous total body irradiation

          -  Known history of HAMA

          -  Chemotherapy or immunotherapy received within the last 4 weeks prior to start of study
             treatment. Pretreatment with rituximab is allowed

          -  Previous hematopoietic stem cell transplantation (autologous and allogenic)

          -  Previous treatment with radioimmunotherapy

          -  Receipt of live, attenuated vaccine within 30 days prior to enrolment

          -  Test positive for hepatitis B (HBsAg and anti-HBc)

          -  A known hypersensitivity to rituximab, HH1, Betalutin or murine proteins or any
             excipient used in rituximab, HH1 or Betalutin

        Part B:

        Inclusion Criteria:

          -  Histologically confirmed (by WHO classification) relapsed non-Hodgkin B-cell FL
             (follicular grade I-IIIA).

          -  Male or female aged ≥ 18 years.

          -  Received at least 2 prior chemotherapy- or immunotherapy-based regimens. Prior therapy
             must include a rituximab/anti-CD20 agent and alkylating agent. Prior exposure to other
             systemic anti-neoplastic agents (including idelalisib or other PI3K inhibitors) is
             also allowed.

          -  Patients must be refractory to any previous regimen containing rituximab/anti-CD20
             agent, defined as no response (no CR or PR) during therapy or a response (CR/PR)
             lasting less than 6 months after the completion of a regimen of rituximab/anti-CD20
             therapy (including occurrence of progressive disease (PD) during rituximab/anti-CD20
             maintenance therapy, or within 6 months of completion of maintenance therapy).

          -  WHO performance status of 0-2.

          -  Life expectancy of ≥ 3 months.

          -  Bone marrow tumour infiltration < 25% (in biopsy taken from a site not previously
             irradiated).

          -  Measurable disease by CT or MRI: longest diameter (LDi) > 1.5 cm for nodal lesion, LDi
             > cm for extra nodal lesion within 28 days prior to start of treatment.

          -  ANC ≥ 1.5 x 109/L.

          -  Platelet count ≥ 150 x 109/L.

          -  Haemoglobin ≥ 9.0 g/dL.

          -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except patients with documented
             Gilbert's syndrome [< 3.0 mg/dL]).

          -  Liver enzymes: Aspartate transaminase (AST); Alanine transaminase (ALT) or ALP ≤ 2.5 x
             ULN (or ≤ 5.0 x ULN with liver involvement by primary disease).

          -  Adequate renal function as demonstrated by a serum creatinine < 1.5 x ULN.

          -  Negative HAMA test at screening.

          -  Negative test at screening for Hepatitis B (negative HBsAG and anti-HBC), Hepatitis C
             and HIV.

        Exclusion Criteria:

          -  Prior hematopoietic allogenic stem cell transplantation.

          -  Prior autologous stem cell transplantation.

          -  Evidence of histological transformation from FL to DLBCL at time of screening.

          -  Previous total body irradiation.

          -  Prior anti-lymphoma therapy (chemotherapy, immunotherapy or other investigational
             agent) within 4 weeks prior to start of study treatment (corticosteroid treatment at
             doses of ≤ 20 mg/day, topical or inhaled corticosteroids, G-CSF or GM-CSF are
             permitted up to 2 weeks prior to start of study treatment). Note: excludes
             pre-treatment with rituximab as part of this study.

          -  Patients with known or suspected CNS involvement of lymphoma.

          -  History of a previous treated cancer except for the following: adequately treated
             local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ,
             superficial bladder cancer, localised prostate cancer undergoing surveillance or
             surgery, localised breast cancer treated with surgery and radiotherapy but not
             including systemic chemotherapy, other adequately treated Stage 1 or 2 cancer
             currently in CR.

          -  Exposure to another CD37 targeting drug.

          -  A known hypersensitivity to rituximab, lilotomab, Betalutin or murine proteins or any
             excipient used in rituximab, lilotomab, or Betalutin.

          -  Has received a live-attenuated vaccine within 30 days prior to enrolment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A, Phase I
Time Frame:12 weeks
Safety Issue:
Description:To define Maximum tolerated dose (MTD) of Betalutin Adverse events and abnormal laboratory values will be graded for toxicity according to CTCAE version 4.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nordic Nanovector

Trial Keywords

  • Radioimmunotherapy
  • Lu-177
  • Phase I study
  • Phase II study
  • Betalutin

Last Updated

September 2, 2019