BI-1206 and an Anti-CD20 Antibody in Patients With CD32b Positive B-cell Lymphoma or Leukaemia

NCT02933320 | Completed Phase 1 Results

• 2 other identifiers: CRUKD160012015-004999-29
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this trial is to identify the tolerable dose of BI-1206 (both alone and in combination) for patients with B-cell lymphoma and leukaemia and further evaluate BI-1206 alone and in combination with an anti-CD20 antibody.

Conditions

B-cell Lymphoma; Chronic Lymphocytic Leukaemia; Waldenström Macroglobulinemia

Keywords

Indolent B-cell Lymphoma; Chronic Lymphocytic Leukaemia; Waldenström Macroglobulinemia; BI-1206; CD32b

Outcome Measures

Primary Outcomes (2)

• Documenting Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) (Graded According to NCI-CTCAE Version 4.02) and Laboratory Parameters and Determining Their Causality in Relation to BI-1206.

  To recommend a dose for future trials with BI-1206 by finding the highest safe dose which can be given to patients.

  Safety data were collected from the date of written informed consent and continued for 125 days after the final administration of BI-1206 or rituximab.

• Documenting AEs, SAEs (Graded According to NCI-CTCAE Version 4.02) and Laboratory Parameters and Determining Their Causality in Relation to BI-1206 and, Where Appropriate, Anti-CD20 Antibody.

  Establishing the MTD or maximum administered dose MAD of BI-1206 and an anti-CD20 antibody given once weekly for four weeks, via intravenous infusion in patients with relapsed or refractory B-cell malignancies.

  Safety data were collected from the date of written informed consent and continued for 125 days after the final administration of BI-1206 or rituximab.

Secondary Outcomes (10)

• Measurement of PK Parameter Maximum Observed Serum Concentration (Cmax) for BI-1206

  Doses 1 and 4 (pre-infusion, end of infusion, +4, +24, +48 and +72 hours)

• Measurement of PK Parameter Area Under the Serum Concentration-time Curve From Time 0 to the Last Time Point (AUClast) for BI-1206

  Doses 1 and 4 (pre-infusion, end of infusion, +4, +24, +48 and +72 hours)

• Measurement of PK Parameter Half-life (T1/2) for BI-1206

  Doses 1 and 4 (pre-infusion, end of infusion, +4, +24, +48 and +72 hours)

• Measurement of PK Parameter Total Body Clearance (CL) for BI-1206

  Doses 1 and 4 (pre-infusion, end of infusion, +4, +24, +48 and +72 hours)

• Measurement of PK Parameter Volume of Distribution (Vss) for BI-1206

  Doses 1 and 4 (pre-infusion, end of infusion, +4, +24, +48 and +72 hours)

Study Arms (4)

Part A: Arm 1: BI-1206 single agent dose escalation phase

EXPERIMENTAL

BI-1206 given by IV infusion to all patients once weekly for a period of four weeks, patients will then have a follow-up period of four weeks (8 week period classified as induction therapy).

Biological: BI-1206 single agent dose escalation phase

Part A: Arm 2: Combination of BI-1206 with rituximab escalation phase

EXPERIMENTAL

Arm 2, an investigation of combination treatment of BI-1206 with rituximab, involving an initial assessment of the appropriate dose of BI-1206 that can be given in combination with rituximab (combination dose escalation cohorts).

Biological: Combination of BI-1206 with rituximab escalation phase

Part B: Arm1: BI-1206 single agent expansion phase

EXPERIMENTAL

Part B Arm 1, an expansion cohort of up to 25 patients treated with single agent BI-1206 at the RP2D as determined in Part A Arm 1. Expansion to include a minimum of 12 chronic lymphocytic leukaemia (CLL) patients and six mantle cell lymphoma (MCL) patients.

Biological: BI-1206 single agent expansion phase

Part B: Arm 2: Combination of BI-1206 with rituximab expansion phase

EXPERIMENTAL

Part B Arm 2, an expansion cohort of up to 25 patients treated with a combination of BI-1206 and rituximab at the RP2D as determined in Part A Arm 2. Expansion to include a minimum of 12 CLL patients and six MCL patients.

Biological: Combination of BI-1206 with rituximab expansion phase

Interventions

BI-1206 single agent dose escalation phase BIOLOGICAL

BI-1206 single agent dose escalation phase to determine the MTD or maximum administered dose (MAD) and recommended Phase II dose (RP2D) for evaluation of BI-1206.

Part A: Arm 1: BI-1206 single agent dose escalation phase

Combination of BI-1206 with rituximab escalation phase BIOLOGICAL

An investigation of combination treatment of BI-1206 with rituximab.

Part A: Arm 2: Combination of BI-1206 with rituximab escalation phase

BI-1206 single agent expansion phase BIOLOGICAL

BI-1206 single agent expansion phase at the RP2D.

Part B: Arm1: BI-1206 single agent expansion phase

Combination of BI-1206 with rituximab expansion phase BIOLOGICAL

BI-1206 in combination with rituximab at the RP2D.

Part B: Arm 2: Combination of BI-1206 with rituximab expansion phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
• B-cell lymphoma or CLL proven by histology or flow cytometry, relapsed or refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient. Patients should have received at least one line of conventional previous therapy which must have included a rituximab based regimen.
• CD32b positive malignancy as demonstrated centrally by immunohistochemistry or flow cytometry prior to study entry. Available tissue or blood must have been taken within six months of study entry.
• Life expectancy of at least 12 weeks.
• World Health Organisation (WHO) performance status of 0-2 (Appendix 1).
• Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before their first dose of mAb (BI-1206 and/or rituximab) as part of this study.
• Laboratory Test Value required
• Haemoglobin (Hb) ≥9.0 g/dL (red cell support is permissible)
• Absolute neutrophil count (ANC) ≥1.0 x 10\^9/L (or \>0.5 x 10\^9/L if due to lymphoma), granulocyte - colony stimulating factor (G-CSF) support is not permissible at screening
• Platelet count ≥50 x 10\^9/L (or ≥30 x 10\^9/L if due to malignant involvement of bone marrow)
• Either:
• Serum bilirubin ≤1.5 x upper limit of normal (ULN) unless raised due to Gilbert's syndrome in which case up to 3 x ULN is permissible.
• Or:
• Alanine amino-transferase (ALT) and /or aspartate amino-transferase (AST) ≤ 2.5 x ULN unless raised due to malignant hepatic involvement in which case up to 5 x ULN is permissible
• Either:

You may not qualify if:

• Allogenic bone marrow transplant within 12 months prior to the first dose of BI-1206 or presence of chronic graft versus host disease.
• Patients with clinically active leptomeningeal or central nervous system lymphoma/leukaemia.
• Doses of prednisolone \>10 mg daily (or equipotent doses of other corticosteroids) are not permitted whilst on the study other than as pre-medication. During the screening period, doses of up to 20 mg per day may be given but the dose must be reduced to 10 mg/day by Cycle 1 Day 1 (or Day -7 in the CLL combination expansion).
• Known or suspected hypersensitivity to study drugs.
• Cardiac or renal amyloid light-chain (AL) amyloidosis.
• Radiotherapy, endocrine therapy, immunotherapy, chemotherapy or investigational medicinal products during the previous 4 weeks before treatment.
• Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Sponsor should not exclude the patient.
• Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two forms of contraception (one highly effective form plus a barrier method) \[oral, injected or implanted hormonal contraception and condom; intra-uterine device and condom; diaphragm with spermicidal gel and condom\] or agree to sexual abstinence\^4 for four weeks before entering the trial, during the trial and for twelve months after completing treatment are considered eligible.
• Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using a barrier method of contraception \[condom plus spermicide\] or to sexual abstinence effective from the first administration of BI-1206 or rituximab on the study, throughout the trial and for twelve months afterwards. Men with partners of child-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intrauterine device, diaphragm with spermicidal gel or sexual abstinence4). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
• Major thoracic or abdominal surgery from which the patient has not yet recovered.
• At high medical risk because of non-malignant systemic disease including infection.
• Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
• Patients with an active, known or suspected autoimmune disease (not including CLL auto-immune disease). Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger will be permitted to participate.
• Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association \[NYHA\]), prior history of cardiac ischaemia or prior history of cardiac arrhythmia.
• Patients for whom rituximab is contraindicated due to severe previous hypersensitivity or any other reason (Arm 2 in Parts A and B \[combination arms\] only).

Sponsors & Collaborators

• Cancer Research UK: lead
• BioInvent International AB: collaborator
• Bloodwise: collaborator

Study Sites (5)

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

Oxford Cancer and Haematology Centre, Churchill Hospital

Oxford, England, OX3 7LE, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, S016 6YD, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, B-Cell; Waldenstrom Macroglobulinemia

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Limitations and Caveats

The trial was terminated early by the Sponsor based on a strategic decision and not a safety related decision. At the time of trial termination, 14 patients had received BI-1206. No patients received rituximab. As a result of the early termination Part B of the trial did not open.

Results Point of Contact

• Title: Regulatory Affairs Manager
• Organization: Cancer Research UK Centre for Drug Development

regulatory@cancer.org.uk

+44 203 4696878

Study Officials

• Andrew Davies, Prof

  University of Southampton

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2016
• First Posted: October 14, 2016
• Study Start: October 27, 2016
• Primary Completion: March 19, 2020
• Study Completion: March 19, 2020
• Last Updated: July 8, 2021
• Results First Posted: July 8, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5)