A Phase I/II Study of Lutetium (177Lu)-Lilotomab Satetraxetan (Betalutin®) Antibody-radionuclide-conjugate for Treatment of Relapsed Non-Hodgkin Lymphoma.
This study is a phase I/II open-label study in patients with relapsed indolent NHL (Part A) or relapsed/refractory FL (Part B). Part A of the study assessed the safety and preliminary efficacy. This seamless design study now has four parts: 1) Part A, Ph I - dose escalation, 2) Part A, Ph II - dose expansion, 3) Part B, Ph II randomized - refinement of dose, and 4) Part B and C, Phase II, single-arm. As of August 7, 2020, patients are enrolling in the fourth part of the study.
‣ 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
‣ Histologically confirmed (by WHO classification) relapsed non-Hodgkin B-cell FL (follicular grade I-IIIA).
• Male or female aged ≥ 18 years. 3. Received at least 2 prior anti-neoplastic or immunotherapy-based regimens (maintenance therapy following a CR/PR is not considered to be a separate line of therapy).
• Prior therapy must include rituximab/anti-CD20 agent and an alkylating agent. Prior exposure to other systemic anti-neoplastic agents (including idelalisib or other phosphatidylinositol 3-kinase (PI3K) inhibitors etc.) is also allowed.
• Patients must be refractory to any previous regimen containing rituximab or an anti-CD20 agent, defined as: no response (no CR/PR) during therapy, or a response (CR/PR) lasting less than 6 months after the completion of a regimen including 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. 7. Life expectancy of ≥ 3 months. 8. 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 > 1.0 cm for extra nodal lesion within 28 days prior to start of treatment.
⁃ ANC ≥ 1.5 x 109/L. 11. Platelet count ≥ 100 x 109/L . 12. Haemoglobin ≥ 9.0 g/dL. 13. 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. 16. Women of childbearing potential must:
‣ understand that the study medication is expected to have teratogenic risk.
‣ have a negative serum beta human-chorionic gonadotropin (ß-HCG) pregnancy test at screening.
‣ commit to continued abstinence from heterosexual intercourse (excluding periodic abstinence or the withdrawal method) or begin a highly effective method of birth control with a Pearl-Index < 1%, without interruption, from 4 weeks before starting study medication, throughout study medication therapy and for 12 months after end of study medication therapy, even if she has amenorrhoea. Apart from abstinence, highly effective methods of birth control are: i. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).
‣ ii. Progestogen-only hormonal contraception associated with inhibition of ovulation ((oral, injectable, implantable) iii. Intrauterine device (IUD). iv. Intrauterine hormone-releasing system (IUS). v. Bilateral tubal occlusion. vi. Vasectomised partner. 17. Male patients must agree to use condoms during intercourse throughout study medication therapy and the following 12 months.
⁃ The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination.
⁃ The patient has been fully informed about the study and has signed the informed consent form.
⁃ Negative HAMA test at screening. 21. Negative Hepatitis B (negative HBsAG and anti-HBC), Hepatitis C and HIV test at screening