Hodgkin LymphomaPhase 1NCT02432235
Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma
A Phase 1 study testing Camidanlumab tesirine in people with Hodgkin Lymphoma and Non-Hodgkin Lymphoma, run by ADC Therapeutics S.A. at 12 sites in 2 countries.
Trial summary
This study evaluates camidanlumab tesirine in participants with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma
- What is being tested?
- Camidanlumab tesirine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 133 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 5 Oct 2015to 24 Oct 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female age 18 years or older.
- Refractory or relapsed lymphoma (per World Health Organization (WHO) Classification system)
- Pathologically confirmed relapsed or refractory lymphoma
- Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
- Measurable disease, defined by the 2014 Lugano Classification Criteria and Global Response Score Grading Scales for cutaneous T-cell lymphoma (CTCL)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Show all 14Show fewer
- Absolute neutrophil count ≥1500/µL. Criterion not applicable to adult T cell leukemia/lymphoma (ATLL) patients.
- Platelet count of ≥75000/µL. Criterion not applicable to ATLL patients.
- Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.
- 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
- 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.
- Total serum/plasma bilirubin ≤1.5 times ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 times ULN)
- Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to Day 1.
- 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.
Who cannot join
- Participants who have an option for any treatment with proven clinical benefit for their lymphoid malignancy at current state of disease.
- Active graft-versus-host disease.
- Autologous or allogenic transplant within the 60 days prior to Cycle 1 Day 1 (C1D1)
- Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
- Known history of positive serum human anti-drug antibody (ADA) or known allergy to any component of ADCT-301.
- 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])
Show all 19Show fewer
- 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).
- 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.
- 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.
- History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
- Pregnant or breastfeeding women.
- 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.
- 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.
- 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.
- 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.
- Congenital long QT syndrome or a corrected QT interval (QTc)≥ 450 ms at screening (unless secondary to pacemaker or bundle branch block).
- 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.
- 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.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States7 sites
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
The University of Texas/MD Anderson Cancer Center
Houston, Texas, 77030-4009
Froedtert Hospital/Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
United Kingdom5 sites
Guy's and St. Thomas' Hospital NHS Trust
London, England, SE1 9RT
The Christie NHS Foundation Trust
Manchester, Greater Manchester, M20 4BX
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, England
Churchill Hospital, Oxford University Hospitals NHS Foundation Trust
Oxford, England, OX3 7LE
Southampton General Hospital, University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire
About this study
Official title: A Phase 1 Adaptive Dose-Escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-301 in Patients With Relapsed or Refractory Hodgkin Lymphoma and Non-Hodgkin Lymphoma
This study evaluates camidanlumab tesirine in participants with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma.
Read the detailed description
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
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma
- Being tested
- Camidanlumab tesirine
- Keywords
- Camidanlumab tesirine
- Medical subject headings
- Hodgkin Disease, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Camidanlumab tesirineDrug
Also called ADCT-301, Cami
Intravenous (IV) infusion.
| Study group | Role | What they receive |
|---|---|---|
| 3 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 5 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 8 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 13 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 20 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 30 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 45 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 60 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 80 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 100 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 150 μg/kg | Experimental | 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. Receives: Drug: Camidanlumab tesirine |
| 300 μg/kg | Experimental | 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). Receives: Drug: Camidanlumab tesirine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
A DLT defined as any of the following, except those that are clearly due to underlying disease or extraneous causes:
A hematologic DLT is defined as (different considerations for Adult T-Cell Leukemia/Lymphoma (ATLL) participants):
- Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 febrile neutropenia or neutropenic infection
- CTCAE Grade 4 neutropenia lasting >7 days
- CTCAE Grade 4 thrombocytopenia
- CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion
- CTCAE Grade 4 anemia
A non-hematologic DLT is defined as:
- CTCAE Grade 4 tumor lysis syndrome
- CTCAE Grade 3 or higher AE (including nausea, vomiting, diarrhea, electrolyte imbalances lasting ≥ 48 hours despite optimal therapy; excluding all grades of alopecia)
- CTCAE Grade 3 or higher hypersensitivity reaction
- CTCAE Grade 2 or higher skin ulceration
- CTCAE Grade 2 or higher peripheral sensory or motor neuropathy
Measured: Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length)
Recommended Dose of Camidanlumab Tesirine for Part 2
The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.
Measured: Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length)
Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Measured: Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days])
Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Measured: Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days])
Secondary outcomes (14)
Overall Response Rate (ORR)
ORR is defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) at the time each participant discontinued treatment with camidanlumab tesirine.
Tumor response was assessed using the 2014 Lugano Classification.
CR is defined as achieving each of the following:
- Complete metabolic response.
- Complete radiologic response (target node regress to <1.5 cm, no nonmeasured lesions, no organ enlargement, no new lesions and normal bone marrow morphology).
PR is defined as achieving each of the following:
- Partial metabolic response (findings indicate residual disease).
- Partial remission (>50% decrease in target measurable nodes, regression/ absence/ no increase of nonmeasured lesions, spleen regressed by >50% in length and no new lesions).
Measured: Day 1 to End of Study (a maximum of 12 months after treatment; median time on treatment was 43 days [min 1 day; max 354 days])
Duration of Response (DoR)
DoR is defined among responders (complete response [CR] and partial response [PR]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification.
Disease progression is defined as progressive metabolic disease and one of the follow:
- Target node progression.
- An individual extranodal lesion must be abnormal with length > 1.5cm and/or increase of length > 50%.
- New or clear progression of nonmeasured lesions.
- Regrowth of previously resolved lesions or new nodes >1.5 cm in length.
- New or recurrent bone marrow involvement.
DoR is presented overall for all participants who were classed as responders among the efficacy analysis set. Data is pooled for all lymphoma participants for DoR as specified in protocol section 8.4.
Measured: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined among the efficacy population as the time from first dose of study drug until either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response.
Disease progression is defined as progressive metabolic disease and one of the following:
- Target node progression.
- An individual extranodal lesion must be abnormal with length > 1.5cm and/or increase of length > 50%.
- New or clear progression of nonmeasured lesions.
- Regrowth of previously resolved lesions or new nodes > 1.5 cm in length.
- New or recurrent bone marrow involvement.
PFS is presented overall for all participants who received camidanlumab tesirine among the efficacy analysis set. Data is pooled for all lymphoma participants for PFS as specified in protocol section 8.4
Measured: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Overall Survival (OS)
Overall survival (OS) is defined as the time from the first dose of study drug treatment until the date of death due to any cause.
OS is presented overall for all participants who received camidanlumab tesirine among the efficacy analysis set. Data is pooled for all lymphoma participants for OS as specified in protocol section 8.4.
Measured: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine
Cmax for HuMax-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC, and free warhead (SG3199).
Measured: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine
Tmax for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Measured: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine
AUC0-last for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Measured: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine
AUC0-tau for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199) for Cycle 2 only.
Measured: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycle 2 (21 day cycle length)
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine
AUC∞ HuMax-TAC and PBD-conjugated HuMax-TAC for Cycle 1 only.
Measured: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycle 1 (21 day cycle length)
Accumulation Index (AI) for Camidanlumab Tesirine
AI for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199). AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1 (21 day cycle length). It is the increase in drug plasma concentration after multiple dosing until a steady state is reached.
Measured: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Volume of Distribution for Camidanlumab Tesirine
Volume of distribution for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Measured: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine
T1/2 of HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Measured: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Clearance of Camidanlumab Tesirine
Clearance of HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).
Measured: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine
An assay determines the presence of anti-ADCT-301 antibodies in human serum using a validated bridging electro chemiluminescence immunoassay (ECLIA) technique. The technique uses the drug itself to capture any anti ADCT-301 antibodies present in the serum. If anti-ADCT-301 antibodies are detected, they are confirmed to be specifically against ADCT-301 and then the level of the anti-ADCT-301 antibodies present in the serum is established using a modified version of the ECLIA technique.
Measured: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2015 (estimated)
- Study start5 Oct 2015
- Primary completion24 Oct 2019
- Study completion24 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 133 participants (actual)
Sponsor and investigators
- Lead sponsor
- ADC Therapeutics S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jens Wuerthner, MD, PhD, Study director, ADC Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02432235
- Sponsor's protocol ID
- ADCT-301-001
- Other IDs
- 2015-005272-25, 199948, 2015
- Status last verified
- Jul 2021
- First submitted
- 26 Feb 2015
- Last updated
- 13 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 36333464Toukam 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.
PubMed 36333463Hamadani 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.
PubMed 34048682
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Adaptive Dose-Escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-301 in Patients With Relapsed or Refractory Hodgkin Lymphoma and Non-Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT02432235
- Acronym / sponsor ID
- ADCT-301-001
- Conditions
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma
- Keywords
- Camidanlumab tesirine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 133 participants (actual)
- Lead sponsor
- ADC Therapeutics S.A.Industry (pharma, biotech, devices)
- Study start
- 5 Oct 2015 (actual)
- Primary completion
- 24 Oct 2019 (actual)
- Study completion
- 24 Oct 2019 (actual)
- First posted
- 4 May 2015 (estimated)
- Results
- Posted 13 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates camidanlumab tesirine in participants with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| 3 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 5 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 8 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 13 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 20 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 30 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 45 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 60 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 80 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 100 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 150 μg/kg | Experimental | Drug: Camidanlumab tesirineParticipants 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. |
| 300 μg/kg | Experimental | Drug: Camidanlumab tesirineA 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male or female age 18 years or older.
- Refractory or relapsed lymphoma (per World Health Organization (WHO) Classification system)
- Pathologically confirmed relapsed or refractory lymphoma
- Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
- Measurable disease, defined by the 2014 Lugano Classification Criteria and Global Response Score Grading Scales for cutaneous T-cell lymphoma (CTCL)
Key exclusion criteria (19 listed)
- Participants who have an option for any treatment with proven clinical benefit for their lymphoid malignancy at current state of disease.
- Active graft-versus-host disease.
- Autologous or allogenic transplant within the 60 days prior to Cycle 1 Day 1 (C1D1)
- Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
- Known history of positive serum human anti-drug antibody (ADA) or known allergy to any component of ADCT-301.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Camidanlumab tesirineAlso: ADCT-301, CamiIntravenous (IV) infusion. | Drug | 100 μg/kg, 13 μg/kg, 150 μg/kg, 20 μg/kg, 3 μg/kg, 30 μg/kg, 300 μg/kg, 45 μg/kg, 5 μg/kg, 60 μg/kg, 8 μg/kg, 80 μg/kg |
Primary outcome
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time frame: Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length)
A DLT defined as any of the following, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as (different considerations for Adult T-Cell Leukemia/Lymphoma (ATLL) participants): * Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 febrile neutropenia or neutropenic infection * CTCAE Grade 4 neutropenia lasting >7 days * CTCAE Grade 4 thrombocytopenia * CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion * CTCAE Grade 4 anemia A non-hematologic DLT is defined as: * CTCAE Grade 4 tumor lysis syndrome * CTCAE Grade 3 or higher AE (including nausea, vomiting, diarrhea, electrolyte imbalances lasting ≥ 48 hours despite optimal therapy; excluding all grades of alopecia) * CTCAE Grade 3 or higher hypersensitivity reaction * CTCAE Grade 2 or higher skin ulceration * CTCAE Grade 2 or higher peripheral sensory or motor neuropathy
Recommended Dose of Camidanlumab Tesirine for Part 2
Time frame: Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length)
The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.
Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days])
An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)
Time frame: Day 1 up to 84 days after last dose (median time on treatment was 43 days [min 1 day; max 354 days])
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
14 secondary outcomes
Overall Response Rate (ORR)
Time frame: Day 1 to End of Study (a maximum of 12 months after treatment; median time on treatment was 43 days [min 1 day; max 354 days])
Duration of Response (DoR)
Time frame: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Progression-Free Survival (PFS)
Time frame: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Overall Survival (OS)
Time frame: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycle 2 (21 day cycle length)
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycle 1 (21 day cycle length)
Accumulation Index (AI) for Camidanlumab Tesirine
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Volume of Distribution for Camidanlumab Tesirine
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Clearance of Camidanlumab Tesirine
Time frame: Pre-dose on Day 1 and 1 to 336 hours post-dose of Cycles 1 and 2 (21 day cycle length)
Number of Participants With Anti-drug Antibody Response (ADA) Against Camidanlumab Tesirine
Time frame: Day 1 to End of Study (a maximum of 12 months after last dose; median time on treatment was 43 days [min 1 day; max 354 days])
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36333464Toukam 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.
- Derived from this study: PubMed 36333463Toukam 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.
- Derived from this study: PubMed 34048682Hamadani 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.
- Individual participant dataSharing planned: No
Related trials for Hodgkin Lymphoma
RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
Active, not recruitingObservational study
Multi-omics Profiling of Relapsed Extranodal Natural Killer (NK)/T-cell Lymphoma
Extranodal NK/T-cell Lymphoma, Nasal Type
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jens Wuerthner, MD, PhD study director
ADC Therapeutics
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Camidanlumab tesirine in people with Hodgkin Lymphoma and Non-Hodgkin Lymphoma, run by ADC Therapeutics S.A. at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (time frame: Cycle 1 Day 1 to end of Cycle 1 or 2 (21 day cycle length)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02432235, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2021.