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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

University Of Arkansas For Medical Sciences
Little Rock, Arkansas 72205

Pacific Shores Medical Group
Long Beach, California 90813
Contact:
Karen Nunez
karenn@pacshoresoncology.com

Boca Raton Regional Hospital
Boca Raton, Florida 33486
Contact:
Sylvie Godbout
561-955-4539
sgodbout@brrh.com

Loyola University Medical Center
Maywood, Illinois 60153
Contact:
Karen Fahey
kfahey@luc.edu

Norton Cancer Institute
Louisville, Kentucky 40207
Contact:
Heather Woolridge
502-899-3366
Heather.Woolridge@nortonhealthcare.org

Ochsner Clinic Foundation
New Orleans, Louisiana 70121
Contact:
Elise Curry
504-842-8084
elisemarie.curry@ochsner.org

Stony Brook University Medical Center
Stony Brook, New York 11794
Contact:
Sebastian Munoz
631-638-0844
Sebastian.Munoz@stonybrookmedicine.edu

Duke University Medical Center
Durham, North Carolina 27710
Contact:
Rachel Stowe
919-681-4769
rachel.stowe@duke.edu

Oregon Health & Science University
Portland, Oregon 97239
Contact:
Libby Mirande
503-494-4740
jenselib@ohsu.edu

University of Pennsylvania
Philadelphia, Pennsylvania 19104
Contact:
Matthew Fillare
215-746-8192
Matthew.Fillare@pennmedicine.upenn.edu

West Penn Hospital
Pittsburgh, Pennsylvania 15224
Contact:
Richard Wonder
412-578-4492
rich.wonder@ahn.org

University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15232
Contact:
Megan Fritz
412-623-8968
fritzm2@upmc.edu

Baylor College of Medicine
Dallas, Texas 75246

More Details

NCT ID
NCT01796171
Status
Recruiting
Sponsor
Nordic Nanovector

Study Contact

Clinical Trials
clinicaltrials@nordicnanovector.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.