Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

NCT ID: NCT02432235

Last Updated: 2021-07-13

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

133 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-05

Study Completion Date

2019-10-24

Brief Summary

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This study evaluates camidanlumab tesirine in participants with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma.

Detailed Description

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This is a Phase I, first in human clinical study with camidanlumab tesirine to evaluate the safety and tolerability and pharmacokinetics of camidanlumab tesirine in participants with relapsed/refractory lymphoma.

Camidanlumab tesirine is a human monoclonal antibody attached via a cleavable linker to a pyrrolobenzodiazepine (PBD) warhead which, when internalized by antigen expressing cells, covalently cross links deoxyribonucleic acid (DNA) preventing replication.

The study will be conducted in 2 parts: Part 1 (dose escalation) and Part 2 (expansion).

Conditions

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Hodgkin Lymphoma Non-Hodgkin Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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3 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (3 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

5 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (5 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 4 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

8 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (8 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

13 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (13 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 15 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

20 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (20 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

30 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (30 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

45 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (45 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

60 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (60 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 8 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

80 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (80 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 7 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

100 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (100 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 5 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

150 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (150 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

300 μg/kg

A single participant received by error an intravenous (IV) infusion of camidanlumab tesirine (300 μg/kg) on Day 1 of Cycle 1 (planned dose was 30 μg/kg). Dosing in the subsequent cycles was 30 μg/kg (for 2 more cycles).

Group Type EXPERIMENTAL

Camidanlumab tesirine

Intervention Type DRUG

Intravenous (IV) infusion.

Interventions

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Camidanlumab tesirine

Intravenous (IV) infusion.

Intervention Type DRUG

Other Intervention Names

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ADCT-301 Cami

Eligibility Criteria

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Inclusion Criteria

1. Male or female age 18 years or older.
2. Refractory or relapsed lymphoma (per World Health Organization (WHO) Classification system)
3. Pathologically confirmed relapsed or refractory lymphoma
4. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
5. Measurable disease, defined by the 2014 Lugano Classification Criteria and Global Response Score Grading Scales for cutaneous T-cell lymphoma (CTCL)
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
7. Absolute neutrophil count ≥1500/µL. Criterion not applicable to adult T cell leukemia/lymphoma (ATLL) patients.
8. Platelet count of ≥75000/µL. Criterion not applicable to ATLL patients.
9. Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.
10. Serum/plasma creatinine ≤1.5 mg/dL, or if the participant has a creatinine \> 1.5 mg/dL, a measured creatinine clearance must be \> 80 mL/min as calculated by the Cockcroft and Gault equation
11. Serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase ≤2 times the upper limit of normal (ULN); ≤ 5 times ULN if there is liver or bone involvement.
12. Total serum/plasma bilirubin ≤1.5 times ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 times ULN)
13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to Day 1.
14. Women of childbearing potential must agree to use a highly effective method of contraception. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception.

Exclusion Criteria

1. Participants who have an option for any treatment with proven clinical benefit for their lymphoid malignancy at current state of disease.
2. Active graft-versus-host disease.
3. Autologous or allogenic transplant within the 60 days prior to Cycle 1 Day 1 (C1D1)
4. Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
5. Known history of positive serum human anti-drug antibody (ADA) or known allergy to any component of ADCT-301.
6. History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis \[e.g., Wegener's granulomatosis\])
7. History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barré syndrome and myasthenia gravis); other central nervous system autoimmune disease (e.g., poliomyelitis, multiple sclerosis).
8. History of recent infection (within 4 weeks of C1D1) considered to be caused by one of the pathogens listed: herpes simplex virus Type 1 (HSV1), herpes simplex virus Type 2 (HSV2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus D68.
9. Known seropositive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV) with confirmatory testing and requiring anti-viral therapy. Note: testing is not mandatory to be eligible.

If participant is at risk for having undiagnosed hepatitis C virus (HCV) (e.g., history of injection drug use), HCV testing should be considered.
10. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
11. Pregnant or breastfeeding women.
12. Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure \> 115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial infarction within 6 months prior to screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
13. Use of any other experimental medication(s) within 14 days or 5 half-lives, but in no case \< 14 days prior to the start of study treatment on Cycle 1, Day 1, except if approved by the Sponsor.
14. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy (including prednisone ≥ 40 mg/day or equivalent) within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except if approved by the Sponsor.
15. Failure to recover (to Common Terminology Criteria for Adverse Events \[CTCAE Version 4.0\] Grade 0 or Grade 1) from acute non-hematologic toxicity (except all grades of alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening.
16. Congenital long QT syndrome or a corrected QT interval (QTc)≥ 450 ms at screening (unless secondary to pacemaker or bundle branch block).
17. Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that Sponsor Medical Monitor and Investigator agree, and document should not be exclusionary.
18. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participant inappropriate for study participation or put the participant at risk.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ADC Therapeutics S.A.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jens Wuerthner, MD, PhD

Role: STUDY_DIRECTOR

ADC Therapeutics

Locations

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City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

The University of Texas/MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Froedtert Hospital/Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Guy's and St. Thomas' Hospital NHS Trust

London, England, United Kingdom

Site Status

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, England, United Kingdom

Site Status

Churchill Hospital, Oxford University Hospitals NHS Foundation Trust

Oxford, England, United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, Greater Manchester, United Kingdom

Site Status

Southampton General Hospital, University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, United Kingdom

Site Status

Countries

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United States United Kingdom

References

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Toukam M, Wuerthner J, Havenith K, Hamadani M, Caimi PF, Kopotsha T, Cruz HG, Boni JP. Population pharmacokinetics analysis of camidanlumab tesirine in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2023 Jan;91(1):13-24. doi: 10.1007/s00280-022-04486-4. Epub 2022 Nov 4.

Reference Type DERIVED
PMID: 36333464 (View on PubMed)

Toukam M, Boni JP, Hamadani M, Caimi PF, Cruz HG, Wuerthner J. Exposure-response analysis of Camidanlumab tesirine in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2023 Jan;91(1):1-12. doi: 10.1007/s00280-022-04487-3. Epub 2022 Nov 4.

Reference Type DERIVED
PMID: 36333463 (View on PubMed)

Hamadani M, Collins GP, Caimi PF, Samaniego F, Spira A, Davies A, Radford J, Menne T, Karnad A, Zain JM, Fields P, Havenith K, Cruz HG, He S, Boni J, Feingold J, Wuerthner J, Horwitz S. Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. Lancet Haematol. 2021 Jun;8(6):e433-e445. doi: 10.1016/S2352-3026(21)00103-4.

Reference Type DERIVED
PMID: 34048682 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-005272-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

199948

Identifier Type: REGISTRY

Identifier Source: secondary_id

ADCT-301-001

Identifier Type: -

Identifier Source: org_study_id

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