A Phase 2 Study to Evaluate the Effectivness and Safety of ADCT-301 in Patients with Relapsed or Refractory Hodgkin Lymphoma

Phase 1

• Conditions: Relapsed or Refractory Hodgkin Lymphoma; MedDRA version: 20.0Level: PTClassification code 10020267Term: Hodgkin's disease refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10020234Term: Hodgkin's disease mixed cellularity refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10020233Term: Hodgkin's disease mixed cellularity recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: LLTClassification code 10080208Term: Classical Hodgkin lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10020328Term: Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002556-32-PL
• Lead Sponsor: ADC Therapeutics SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-09-12
• Last Update Posted: 3 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

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 (ß-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.

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, 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,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified