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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2015 by Nordic Nanovector
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
Nordic Nanovector
ClinicalTrials.gov Identifier:
NCT01796171
First received: February 19, 2013
Last updated: January 5, 2016
Last verified: December 2015
  Purpose
This study is a phase I/II, open-label study in patients with relapsed positive non-Hodgkin lymphoma. The Phase I part of the study is a dose escalating study to define the maximum tolerable dose of 177Lu-DOTA-HH1 (Betalutin), assess safety and toxicity, pharmacokinetics, biodistribution and efficacy. After completion of the phase I study, a dose will be selected for the phase II part of the study which is designed to investigate tumour response rate, progression free survival, confirmation of the selected dose as well as safety and toxicity.

Condition Intervention Phase
Non-Hodgkin Lymphoma
Drug: Betalutin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of 177Lu-HH1 (Betalutin®) Radioimmunotherapy for Treatment of Relapsed Non-Hodgkin Lymphoma.

Resource links provided by NLM:


Further study details as provided by Nordic Nanovector:

Primary Outcome Measures:
  • Safety/Dose limiting toxicity [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

    Patients are closely monitored during and after injection of Betalutin over a 12 week period. Thereafter, at certain intervals up to 5 years. Safety evaluations are vital signs, physical examination, hematology and serum biochemistry.

    Adverse events and abnormal laboratory values will be graded for toxicity according to CTCAE version 4.



Secondary Outcome Measures:
  • Efficacy [ Time Frame: 3 months - 5 years ] [ Designated as safety issue: No ]
    CT or PET/CT imaging will be used to quantify changes in lesions on baseline imaging, with responses classified according to revised response criteria for NHL (Cheson, 2007.)


Estimated Enrollment: 49
Study Start Date: December 2012
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: With HH1 pre-dosing
Betalutin, 10 MBq/kg b.w. in escalated doses with HH1 pre-dosing.
Drug: Betalutin
Dose finding study, starting on 10 MBq/kg b.w. Betalutin (177Lu-Dota-HH1), single injection.
Experimental: Without pre-dosing
Betalutin, 15 MBq/kg b.w. in escalated doses without pre-dosing.
Drug: Betalutin
Dose finding study, starting on 10 MBq/kg b.w. Betalutin (177Lu-Dota-HH1), single injection.
Experimental: With rituximab pre-dosing
Betalutin, 15 MBq/kg b.w. in escalated doses with rituximab pre-dosing.
Drug: Betalutin
Dose finding study, starting on 10 MBq/kg b.w. Betalutin (177Lu-Dota-HH1), single injection.
Experimental: Different HH1 pre-dosing regimen
Betalutin, 15 MBq/kg b.w. in escalated doses with a different HH1 pre-dosing regimen.
Drug: Betalutin
Dose finding study, starting on 10 MBq/kg b.w. Betalutin (177Lu-Dota-HH1), single injection.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Age ≥ 18 years
  3. A pre-study WHO performance status of 0-1
  4. Life expectancy should be ≥ 3 months
  5. <25% tumour cells in bone marrow biopsy
  6. Measurable disease by radiological methods
  7. Women of childbearing potential must:

    1. understand that the study medication is expected to have teratogenic risk
    2. have a negative pregnancy test
    3. agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy and for 12 months after end of study drug therapy, even if she has amenorrhoea
  8. Male subjects must agree to use condoms during intercourse throughout study drug therapy and the following 12 months
  9. Patients previously treated with native rituximab are eligible
  10. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination
  11. The patient has been fully informed about the study and has signed the informed consent form

Exclusion Criteria:

  1. Medical contraindications, including uncontrolled infection, severe cardiac, pulmonary, neurologic, psychiatric or metabolic disease, steroid requiring asthma/allergy, known HIV positive
  2. Laboratory values within 15 days pre-registration:

    1. Absolute Neutrophil Counts (ANC) ≤ 1.5 x 109 /l
    2. Platelet count ≤ 150 x 109 /l
    3. Total bilirubin ≥ 30 mmol/l
    4. ALP and ALAT ≥ 4x normal level)
    5. Creatinine ≥ 115 µmol/l (men), 97 µmol/l (women))
    6. IgG ≤ 3 gr/l
  3. Known CNS involvement of lymphoma
  4. Previous total body irradiation, or irradiation of > 25% of the patient's bone marrow
  5. Known history of HAMA
  6. Chemotherapy or immunotherapy received within the last 4 weeks prior to start of study treatment. Pretreatment with rituximab is allowed
  7. Pregnant or lactating women
  8. Previous hematopoietic stem cell transplantation (autologous and allogenic)
  9. Previous treatment with radioimmunotherapy
  10. Actively participating in another study or received an investigational drug within 4 weeks prior to enrolment
  11. Receipt of live, attenuated vaccine within 30 days prior to enrolment
  12. Test positive for hepatitis B (HBsAg and anti-HBc)
  13. A known hypersensitivity to rituximab, HH1, Betalutin or murine proteins or any excipient used in rituximab, HH1 or Betalutin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01796171

Contacts
Contact: Laurie Baylor Curtis +44 7557806472 lbaylorcurtis@nordicnanovector.com

Locations
Austria
Not yet recruiting
Innsbruck, Austria, 6020
Recruiting
Linz, Austria, 4020
Not yet recruiting
Wien, Austria, 1090
Czech Republic
Not yet recruiting
Brno, Czech Republic, 625 00
Recruiting
Olomouc, Czech Republic, 779 00
Not yet recruiting
Ostrava-Poruba, Czech Republic, 708 52
Not yet recruiting
Praha, Czech Republic, 12 08
Italy
Recruiting
Bologna, Italy, 40138
Not yet recruiting
Firenze, Italy, 50134
Not yet recruiting
Genova, Italy, 16132
Norway
Recruiting
Oslo, Norway, 0310
Recruiting
Trondheim, Norway, 7006
Poland
Recruiting
Krakow, Poland, 50-510
Not yet recruiting
Warszawa, Poland, 02-097
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
  More Information

Publications:
Responsible Party: Nordic Nanovector
ClinicalTrials.gov Identifier: NCT01796171     History of Changes
Other Study ID Numbers: EudraCT: 2011-000033-36 
Study First Received: February 19, 2013
Last Updated: January 5, 2016
Health Authority: Austria: Austrian Federal Office for Safety in Health Care
Austria: Ethikkommission
Czech Republic: State Institute for Drug Control
Czeck Republic: Central Ethics Committee of the Ministry of Health of the Czech Republic
Italy: The Italian Medicines Agency
Italy: Ethics Committee
Norway: Norwegian Medicines Agency
Norway: Regional Ethics Commitee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ethics Committee
Sweden: Medical Products Agency
Sweden: Central Ethical Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2016