E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Hodgkin Lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080208 |
E.1.2 | Term | Classical Hodgkin lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020328 |
E.1.2 | Term | Hodgkin's lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020267 |
E.1.2 | Term | Hodgkin's disease refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020234 |
E.1.2 | Term | Hodgkin's disease mixed cellularity refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020233 |
E.1.2 | Term | Hodgkin's disease mixed cellularity recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the efficacy of single agent camidanlumab tesirine in patients with relapsed or refractory Hodgkin Lymphoma |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives
Characterize additional efficacy endpoints of camidanlumab tesirine
Characterize the safety profile of camidanlumab tesirine
Characterize the PK profile of camidanlumab tesirine
Evaluate the immunogenicity of camidanlumab tesirine
Evaluate the impact of camidanlumab tesirine treatment on health-related quality of life (HRQoL) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained prior to any procedures.
2. Male or female patients aged 18 years or older.
For US sites only: Male or female patients aged 16 years or older.
3. Pathologic diagnosis of cHL.
4. Patients with relapsed or refractory cHL, who have received at least 3 prior lines of systemic therapy (or at least 2 prior lines in HSCT ineligible patients) including brentuximab vedotin and a checkpoint inhibitor approved for cHL (e.g., nivolumab or pembrolizumab).
Note 1: Receipt of HSCT to be included in the number of prior therapies needed to meet eligibility.
Note 2: The reason(s) for HSCT ineligibility must be documented in the patient medical records/source documents and eCRF.
5. Measurable disease as defined by the 2014 Lugano Classification.
6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available).
Note 1: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred.
Note 2: If a sufficient amount of tissue is not available, a fresh biopsy
may be taken, provided the procedure is not deemed high-risk and is
clinically feasible, and provided it is approved locally.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
8. Adequate organ function as defined by Screening laboratory values within the following parameters:
a. Absolute neutrophil count (ANC) ≥ 1.0 × 10^3/μL (off growth factors at least 72 h).
b. Platelet count ≥ 75 × 10^3/μL without transfusion in the past 2 weeks.
c. ALT, AST, or GGT ≤ 2.5 × the upper limit of normal (ULN) if there is no liver involvement; ALT or AST ≤ 5 × ULN if there is liver involvement.
d. Total bilirubin ≤ 1.5 × ULN (patients with known Gilbert’s syndrome may have a total bilirubin up to ≤ 3 × ULN with direct bilirubin ≤ 1.5 × ULN).
e. Blood creatinine ≤ 3.0 × ULN or calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault equation.
Note: A laboratory assessment may be repeated a maximum of two times during the Screening Period to confirm eligibility.
9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug for women of childbearing potential.
10. Women of childbearing potential (WOCBP)* must agree to use a highly effective** method of contraception from the time of giving informed consent until at least 6.5 months after the last dose of camidanlumab tesirine. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 16 weeks after the patient receives his last dose of camidanlumab tesirine.
* Women of childbearing potential are defined as sexually mature women who have not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or who have not been postmenopausal.
A postmenopausal state is defined as no menses for 12 months without
an alternative medical cause. A high follicle stimulating hormone (FSH)
level in the postmenopausal range may be used to confirm a
postmenopausal state in women not using hormonal contraception or
hormonal replacement therapy. However, in the absence of 12 months of
amenorrhea, a single FSH measurement is insufficient.
** Highly effective forms of birth control are methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Highly effective forms of birth control include: hormonal contraceptives associated with inhibition of ovulation (oral, injectable, patch and intrauterine devices), male partner sterilization, or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the patient.
Note: The double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, postovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and spermicide-only are not acceptable as highly effective methods of contraception. |
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E.4 | Principal exclusion criteria |
1. Previous treatment with camidanlumab tesirine.
2. Participation in another investigational interventional study. Being in follow-up of another investigational study is allowed.
3. Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA) to a CD25 antibody.
4. Allogenic or autologous HSCT within 60 days prior to start of study drug.
5. Active graft-versus-host disease (GVHD), except for non-neurologic symptoms as a manifestation of mild (≤ Grade 1) chronic GVHD.
6. Post-HSCT lymphoproliferative disorders.
7. Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor’s medical monitor and Investigator agree and document should not be exclusionary.
8. 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]) (subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition only requiring hormone replacement may be enrolled).
9. History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barré syndrome and myasthenia gravis) or other central nervous system autoimmune disease (e.g., poliomyelitis, multiple sclerosis).
10. History of recent infection (within 4 weeks of C1D1) considered to be caused by one of the following pathogens: HSV1, HSV2, VZV, EBV, CMV, measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus D68, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Note: An influenza test and a pathogen-directed SARS-CoV-2 test (such as polymerase chain reaction [PCR]) are mandatory and must be negative before initiating study treatment (tests to be performed 3 days or less prior to dosing on C1D1); an additional 2 days are allowed in the event of logistical issues for receiving the results on time).
11. Patients who are carriers of human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV), and require antiviral therapy or prophylaxis.
Note: Serology testing is mandatory for patients with unknown status.
12. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
13. Failure to recover ≤ Grade 1 (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v4.0]) from acute non-hematologic toxicity (except ≤ Grade 2 neuropathy or alopecia), due to previous therapy, prior to screening.
14. HL with central nervous system involvement, including leptomeningeal disease.
15. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath).
16. Breastfeeding or pregnant.
17. Significant medical comorbidities, including uncontrolled hypertension (blood pressure [BP] ≥ 160/100 mmHg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 3 months prior to screening, severe uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease.
18. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drug, except shorter if approved by the Sponsor.
19. Use of any other experimental medication within 30 days prior to start of study drug.
20. Any live vaccine within 4 weeks prior to start of study drug and planned live vaccine administration after starting study drug.
21. Congenital long QT syndrome, or a corrected QTc interval of ≥ 480 ms, at screening (unless secondary to pacemaker or bundle branch block).
22. Any other significant medical illness, abnormality, or condition that would, in the Investigator’s judgment, make the patient inappropriate for study participation or put the patient at risk. |
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR according to the 2014 Lugano classification as determined by central review in all-treated patients
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline (screening), 6 weeks post-dose, 12 weeks post-dose, then every 9 weeks until EOT. If no progression at EOT, then every 12 weeks for 1 year post-EOT, then every 6 months until disease progression. |
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E.5.2 | Secondary end point(s) |
- DOR defined as the time from the first documentation of tumor response to disease progression or death
- CR rate defined as the percentage of treated patients with a best overall response (BOR) of CR
- Relapse-free survival (RFS) defined as the time from the documentation of CR to disease progression or death
- Progression-free survival (PFS) defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause
- Overall survival (OS) defined as the time from first dose of study drug until death due to any cause
- Fraction of patients receiving hematopoietic stem cell transplant (HSCT).
- Frequency and severity of AEs and SAEs
- Changes from Baseline of safety laboratory values, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, and 12-lead electrocardiograms (ECGs)
- Concentrations and PK parameters of camidanlumab tesirine total antibody, pyrrolobenzodiazepine (PBD)-conjugated antibody, and unconjugated warhead SG3199
- Frequency of confirmed positive anti-drug antibody (ADA) responses, their associated ADA titers and, if applicable, neutralizing activity to camidanlumab tesirine after treatment with camidanlumab tesirine
- Change from Baseline in HRQoL as measured by EuroQoL–5 Dimensions–5 Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
DOR, CR rate, RFS, PFS: From baseline (screening), 6 weeks post-dose, 12 weeks post-dose, then every 9 weeks until EOT. If no progression at EOT, then every 12 weeks for 1 year post-EOT, then every 6 months until disease progression.
Fraction of patients receiving HSCT, OS: from baseline (screening) until End of study.
AE/SAE: From informed consent signature until EOT or maximum of 30 days after last dose, thereafter only SAEs when related to study medication.
ECOG, ECGs, PK, ADA, EQ-5D-5L, FACT-Lym: From Day one assessment/sample collection through multiple days across cycles until EOT. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 66 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United States |
Belgium |
Czechia |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |