An early phase clinical trial testing a new antibody (BI-1206) for use with rituximab in patients with slow-growing types of Non-Hodgkin Lymphoma that has not responded to or has returned after previous treatment with rituximab

Phase 1

Conditions: Indolent B-Cell Non-Hodgkin Lymphoma
MedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-000444-26-PL

Lead Sponsor: BioInvent International AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 52

Inclusion Criteria

1. Are = 18 years of age by initiation of study treatment.
2. Provide written (signed and dated) informed consent.
3. Are capable of cooperating with treatment and follow-up.
4. Have B-cell NHL proven by histology, with histological subtypes limited to FL (except FL3B), MCL and MZL.
5. Have measurable nodal disease, defined as the presence of =1 nodal lesion that measures =1.5 cm in a single dimension as assessed by computerized tomography (CT) or magnetic resonance imaging (MRI).
6. Are willing to undergo lymph node biopsies or biopsies of other involved tissue (besides bone marrow). However, if the investigator feels that a tissue biopsy is not technically feasible, then the subject will not be required to undergo biopsies. If viable frozen tissue (not formalin-fixed) from a previous standard of care biopsy in the previous 8 weeks prior to consent is available, a new biopsy at screening is not required.
7. Have relapsed disease or disease refractory to conventional treatment or for which no standard therapy exists, the investigator judges available standard therapy as not being appropriate for the subject, or is declined by the subject. Rituximab refractory disease is defined as:
• Lack of CR or PR during rituximab-containing treatment comprising =2 doses of =375 mg/m2, or
• Occurrence of progressive disease after completion of a regimen of rituximab-containing therapy comprising =2 doses of =375 mg/m2, or
• Occurrence of progressive disease during rituximab maintenance therapy or within 6 months of completion of rituximab maintenance therapy.
8. Have received at least one line of conventional previous therapy which must include at least one rituximab-based regimen.
9. Have a life expectancy of at least 12 weeks on the day of the first infusion of BI-1206.
10. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2.
11. Have CD20+ malignancy as demonstrated by IHC or flow cytometry prior to first dose of BI-1206. Analysis must have been performed on tissue obtained within 6 months of signature of the informed consent form (ICF); otherwise, a new biopsy is required.
12. Have hematological and biochemical indices within prespecified ranges, including hemoglobin (=9.0 g/dL, red cell support is permissible); absolute neutrophil count (ANC) (=1.0 × 109/L, or >0.5 × 109/L if due to lymphoma; granulocyte-colony stimulating factor support is not permissible at screening); and platelet count (=100 × 109/L). These measurements must be performed within 1 week and assessed by the Investigator before their first dose of BI-1206.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

Exclusion Criteria

1. Have had an allogenic bone marrow or stem cell transplant within 12 months prior to the first dose of BI-1206.
2. Have presence of active chronic graft versus host disease of any grade/severity.
3. Have current leptomeningeal lymphoma or compromise of the central nervous system.
4. Have transformed lymphoma from a pre-existing indolent lymphoma. Subjects with a previous history of transformation, but on this disease episode have a biopsy proven indolent recurrence, may be included. Subjects with proven or suspected Richter transformation are not eligible.
5. Have Waldenstrom’s Macroglobulinemia or FL3B, due to the high risk of transformation while on study.
6. Need systemic doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the study other than as pre-medication. During the screening period, doses of up to 20 mg/day may be given but the dose must be reduced to 10 mg/day within 7 days prior the first dose of study drug. Inhaled or intranasal steroids are permissible.
7. Have known or suspected hypersensitivity to rituximab or BI-1206. Previous isolated IRRs are not to be considered a reason for exclusion.
8. Have cardiac or renal amyloid light-chain amyloidosis.
9. Have received any of the following:
• Chemotherapy or small molecule products with 2 weeks of first dose of BI- 1206 and/or
• Radiotherapy (except for focal symptomatic control of lymphadenopathy) within 4 weeks of first dose of BI-1206 and/or
• Immunotherapy within 8 weeks prior to the first dose of BI-1206.
10. Have ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator should not exclude the subject.
11.Have the ability to become pregnant (or already pregnant or lactating/breastfeeding). However, those female subjects who have a negative serum pregnancy test before enrollment and agree to use a highly effective method of birth control for 4 weeks before entering the trial, during the trial and for 12 months after last dose of BI 1206 are considered eligible. Highly effective methods of birth control include:
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation
• Progestogen-only hormonal contraception associated with inhibition of ovulation
• Intrauterine device
• Intrauterine hormone-releasing system
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence
12. Are male subjects with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception (condom plus spermicide gel) during the trial and for 12 months after completing treatment). Men with pregnant or lactating partners should be advised to use barrier method contraception (condom plus spermicidal gel) to prevent exposure to the fetus or neonate.
13. Have had major surgery from which the subject has not yet recovered.
14. Are at high medical risk because of non-malignant systemic disease including active infection on treatment with antibiotics, antifungals or antivirals.
15. Are serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
16. Have an active, known or suspected autoimmune disease. However, subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia not requiring

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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