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A Phase I/II Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma (LYMRIT-37-01)

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ClinicalTrials.gov Identifier: NCT01796171
Recruitment Status : Recruiting
First Posted : February 21, 2013
Last Update Posted : April 13, 2018
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
Nordic Nanovector

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-Hodgkin Lymphoma Follicular Lymphoma Drug: Betalutin Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 207 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Lutetium (177Lu)-Lilotomab Satetraxetan (Betalutin®) Antibody-radionuclide-conjugate for Treatment of Relapsed Non-Hodgkin Lymphoma.
Actual Study Start Date : December 2012
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Part A, Arm 1: with lilotomab pre-dosing
Betalutin, 10 MBq/kg b.w. in escalated doses with lilotomab pre-dosing.
Drug: Betalutin
Betalutin, 10 MBq/kg b.w. in escalated doses with 40 mg lilotomab pre-dosing
Experimental: Part A, Arm 2: without pre-dosing
Betalutin, 15 MBq/kg b.w. in escalated doses without pre-dosing.
Drug: Betalutin
Betalutin, 15 MBq/kg b.w. in escalated doses without pre-dosing
Experimental: Part A, Arm 3: with rituximab pre-dosing
Betalutin, 15 MBq/kg b.w. in escalated doses with rituximab pre-dosing.
Drug: Betalutin
Betalutin, 15 MBq/kg b.w. in escalated doses with rituximab pre-dosing
Experimental: Part A, Arm 4: with higher dose lilotomab pre-dosing
Betalutin, 15 MBq/kg b.w. in escalated doses with a higher dose lilotomab pre-dosing regimen.
Drug: Betalutin
Betalutin, 15 MBq/kg b.w. in escalated doses with 100 mg/m2 lilotomab pre-dosing
Experimental: Part A, Arm 5: with intermediate dose lilotomab pre-dosing
Betalutin, 20 MBq/kg b.w. with an intermediate dose lilotomab pre-dosing regimen.
Drug: Betalutin
Betalutin, 20 MBq/kg b.w. in escalated doses with 60 mg/m2 lilotomab pre-dosing
Experimental: Part B
Betalutin, 15 MBq/kg b.w. with 40mg lilotomab compared to Betalutin, 20 MBq/kg b.w. with 100mg/m2 lilotomab
Drug: Betalutin
Betalutin, 15 MBq/kg b.w. with 40mg lilotomab compared to Betalutin, 20 MBq/kg b.w. with 100 mg/m2 lilotomab



Primary Outcome Measures :
  1. Part A, Phase I [ Time Frame: 12 weeks ]
    To define Maximum tolerated dose (MTD) of Betalutin Adverse events and abnormal laboratory values will be graded for toxicity according to CTCAE version 4.

  2. Part A, Phase IIa [ Time Frame: 3 months - 5 years ]
    To explore tumour response rates in patients receiving Betalutin

  3. Part B, Phase IIb [ Time Frame: 3 months - 5 years ]
    Overall response rate



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 idelalisib or other PI3K inhibitors is also allowed.
  • Patients must be refractory to the last rituximab/anti-CD20 based treatment, 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). A previous regimen is defined as one of the following: at least 2 months of single agent therapy; at least 2 consecutive cycles of chemotherapy.
  • 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: 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01796171


Contacts
Contact: Clinical Trials clinicaltrials@nordicnanovector.com

Locations
Austria
Recruiting
Innsbruck, Austria, 6020
Not yet recruiting
Wien, Austria, 1090
Croatia
Not yet recruiting
Zagreb, Croatia
Czechia
Recruiting
Olomouc, Czechia, 779 00
Recruiting
Ostrava-Poruba, Czechia, 708 52
Italy
Not yet recruiting
Bologna, Italy, 40138
Not yet recruiting
Firenze, Italy, 50134
Norway
Not yet recruiting
Bergen, Norway
Not yet recruiting
Oslo, Norway, 0310
Not yet recruiting
Trondheim, Norway, 7006
Poland
Recruiting
Krakow, Poland, 50-510
Recruiting
Warszawa, Poland, 02-097
Spain
Recruiting
Madrid, Spain
Recruiting
Salamanca, Spain
Sweden
Recruiting
Borås, Sweden, 50455
Recruiting
Linköping, Sweden, 581 85
Recruiting
Umeå, Sweden
United Kingdom
Recruiting
Poole, Dorset, United Kingdom, BH15 2JB
Recruiting
Bristol, United Kingdom, BS2 8ED
Recruiting
Glasgow, United Kingdom, G12 0YN
Recruiting
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Nordic Nanovector
ICON Clinical Research
Investigators
Principal Investigator: Arne Kolstad, MD, PhD Oslo University Hospital

Publications:
Responsible Party: Nordic Nanovector
ClinicalTrials.gov Identifier: NCT01796171     History of Changes
Other Study ID Numbers: EudraCT: 2011-000033-36
First Posted: February 21, 2013    Key Record Dates
Last Update Posted: April 13, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nordic Nanovector:
Radioimmunotherapy
Lu-177
Phase I study
Phase II study
Betalutin

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents