Safety and Tolerability of BAY1862864 Injection in Subjects With Relapsed or Refractory CD22-positive Non-Hodgkin's Lymphoma

NCT ID: NCT02581878

Last Updated: 2020-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-20

Study Completion Date

2019-11-26

Brief Summary

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To establish a recommended dose of BAY1862864 Injection and to investigate how the study drug acts in the body, on the cancer cells and how safe it is in patients with advanced non-Hodgkin's lymphoma (NHL)

Detailed Description

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The study will be divided into two parts: a "dose-escalation part" to evaluate safety profile and to explore the Maximum tolerated dose (MTD) and an "expansion part" to evaluate further the safety and tumor response profile of BAY1862864 Injection at the selected dose.

Conditions

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Lymphoma, Non-Hodgkin

Keywords

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Thorium-227 BAY1862864 Injection Safety Pharmacokinetics CD22 Radioimmunotherapy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1a

Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 1.5 MBq (2 mg antibody chelator conjugate \[ACC\]).

Group Type EXPERIMENTAL

BAY1862864

Intervention Type DRUG

Radiopharmaceutical, injection: Up to four treatment cycles lasting six weeks each; in each cycle, a single treatment on Day 1. In this dose-escalation part of the study, the radioactivity dose will start at 1.5 MBq and increase in steps of 1.5 MBq, with a antibody-chelator conjugate dose of 2 or 10 mg.

Cohort 1b

Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 1.5 MBq (10 mg ACC).

Group Type EXPERIMENTAL

BAY1862864

Intervention Type DRUG

Radiopharmaceutical, injection: Up to four treatment cycles lasting six weeks each; in each cycle, a single treatment on Day 1. In this dose-escalation part of the study, the radioactivity dose will start at 1.5 MBq and increase in steps of 1.5 MBq, with a antibody-chelator conjugate dose of 2 or 10 mg.

Cohort 2

Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 3.1 MBq (10 mg ACC).

Group Type EXPERIMENTAL

BAY1862864

Intervention Type DRUG

Radiopharmaceutical, injection: Up to four treatment cycles lasting six weeks each; in each cycle, a single treatment on Day 1. In this dose-escalation part of the study, the radioactivity dose will start at 1.5 MBq and increase in steps of 1.5 MBq, with a antibody-chelator conjugate dose of 2 or 10 mg.

Cohort 3

Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 4.6 MBq (10 mg ACC).

Group Type EXPERIMENTAL

BAY1862864

Intervention Type DRUG

Radiopharmaceutical, injection: Up to four treatment cycles lasting six weeks each; in each cycle, a single treatment on Day 1. In this dose-escalation part of the study, the radioactivity dose will start at 1.5 MBq and increase in steps of 1.5 MBq, with a antibody-chelator conjugate dose of 2 or 10 mg.

Cohort 4

Cancer patients with relapsed or refractory non-Hodgkin's lymphoma will be randomized to receive an injection of study drug (BAY1862864) with a dosage of 6.1 MBq (10 mg ACC).

Group Type EXPERIMENTAL

BAY1862864

Intervention Type DRUG

Radiopharmaceutical, injection: Up to four treatment cycles lasting six weeks each; in each cycle, a single treatment on Day 1. In this dose-escalation part of the study, the radioactivity dose will start at 1.5 MBq and increase in steps of 1.5 MBq, with a antibody-chelator conjugate dose of 2 or 10 mg.

Interventions

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BAY1862864

Radiopharmaceutical, injection: Up to four treatment cycles lasting six weeks each; in each cycle, a single treatment on Day 1. In this dose-escalation part of the study, the radioactivity dose will start at 1.5 MBq and increase in steps of 1.5 MBq, with a antibody-chelator conjugate dose of 2 or 10 mg.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Subject has relapsed or refractory CD22-positive histologically confirmed NHL
* An archival paraffin-embedded tissue or fresh biopsy is available for the retrospective quantitative assessment of CD22 levels
* Bone marrow involvement of cellular marrow with lymphoma determined to be \< 25%
* Subject has failed at least one prior chemo-/immunotherapy-based regimen
* Life expectancy of at least 12 weeks
* Not eligible for, or refused, or failed high-dose therapy combined with autologous stem cell rescue (HDT ASCR)
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
* Women of childbearing potential must have negative pregnancy test within seven days before the start of treatment
* Subject was using adequate barrier birth control measures before the study and is willing to continue use of these during the entire course of the study and for the twelve months after the last administration of BAY1862864 Injection
* Adequate bone-marrow, hepatic and renal function
* Subject is capable of giving informed consent and has provided such consent in writing

Exclusion Criteria

* Previous exposure to the study drug. Previous exposure to CD22 antibody within six months before screening. Any radio-immunotherapy within six months before screening.
* History of anaphylactic reactions to monoclonal antibody therapy. Known or suspected allergy or intolerance to any agent to be given in the course of this study.
* Anti-cancer immunotherapy and/or anti cancer chemotherapy within four weeks before the first dose of study drug
* Previous therapy with fludarabine-containing regimens within three months before screening
* Participation in any other clinical trial in which the subject received active therapy within four weeks before the first scheduled dose of study drug
* Any toxic effects (CTCAE ≥ Grade 2) of previous anti cancer therapy (incl. radiotherapy) that have not yet stabilized or significant post-treatment toxicities have been observed
* Prior definitive radiotherapy completed less than four weeks before the date scheduled for first dose of BAY1862864
* History of symptomatic metastatic brain or meningeal tumors. Presence of new or progressive brain metastases.
* History of clinically significant cardiac disease
* Clinically relevant findings in the ECG.
* Uncontrolled hypertension, defined as systolic blood pressure \> 160 mmHg and / or diastolic blood pressure \> 100 mmHg, despite optimum medical management
* History of arterial or venous thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or clinically relevant pulmonary embolism within three months before the first administration of BAY1862864 (except for adequately treated catheter-related venous thrombosis occurring more than one month before start of study medication)
* Autologous bone-marrow transplant or stem-cell rescue within three months before the first administration of BAY1862864
* Organ allograft (except for corneal transplant) or allogeneic bone-marrow transplant at any time before the first administration of BAY1862864
* Positive result of hepatitis B virus (HBV-DNA) and/or human immunodeficiency virus antibody (HIV-Ab) test
* Liver cirrhosis, defined as Child-Pugh class B or C
* Any active infection of CTCAE Grade ≥2
* Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study
* Major surgery or significant trauma within four weeks before the first administration of BAY1862864
* Any treatment with biological response modifiers (such as, but not limited to, granulocyte colony-stimulating factor, G CSF), or any blood transfusion, within three weeks before first administration of BAY1862864
* Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study result
* Current pregnancy or breast-feeding
* Any condition that is unstable or could jeopardize the safety of the subject and his/her compliance with study requirements
* Close affiliation with the investigation site
* Any use by the subject of illicit drugs or other substances that may, in the opinion of the investigator or his/her designated associate(s), have a reasonable chance of contributing to toxicity or otherwise confound the results
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

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Skanes Universitetssjukhus

Lund, , Sweden

Site Status

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Site Status

Royal Marsden NHS Trust (Surrey)

Sutton, Surrey, United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

Countries

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Austria Finland Germany Sweden United Kingdom

References

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Linden O, Bates AT, Cunningham D, Hindorf C, Larsson E, Cleton A, Pinkert J, Huang F, Bladt F, Hennekes H, Oedegaardstuen LI, Sturm I, McNamara C. 227Th-Labeled Anti-CD22 Antibody (BAY 1862864) in Relapsed/Refractory CD22-Positive Non-Hodgkin Lymphoma: A First-in-Human, Phase I Study. Cancer Biother Radiopharm. 2021 Oct;36(8):672-681. doi: 10.1089/cbr.2020.4653. Epub 2021 Apr 21.

Reference Type DERIVED
PMID: 33887152 (View on PubMed)

Related Links

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http://clinicaltrials.bayer.com/

Click here to find results for studies related to Bayer products

http://www.clinicaltrialsregister.eu/

Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Other Identifiers

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2014-004140-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17845

Identifier Type: -

Identifier Source: org_study_id