Clinical Trials /

Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma

NCT04052997

Description:

The purpose of this study is to evaluate the clinical efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin Lymphoma (HL).

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma
  • Official Title: A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: ADCT-301-201
  • NCT ID: NCT04052997

Conditions

  • Relapsed Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Camidanlumab TesirineADCT-301Camidanlumab Tesirine

Purpose

The purpose of this study is to evaluate the clinical efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin Lymphoma (HL).

Detailed Description

      This is a phase 2, multi-center, open-label, single-arm study of efficacy and safety of
      Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin
      lymphoma. This study will enroll approximately 100 participants.

      Camidanlumab Tesirine (ADCT-301) is an antibody drug conjugate (ADC), composed of the human
      monoclonal antibody, HuMax®-TAC, which is directed against human CD25. The antibody is
      conjugated through a protease cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer
      cytotoxin.

      For each participant the study will include a screening period (of up to 28 days), a
      treatment period (cycles of 3 weeks), and a follow-up period (approximately every 12-week
      visits) for up to 3 years after treatment discontinuation.

      Participants may continue treatment for up to 1 year or until disease progression,
      unacceptable toxicity, or other discontinuation criteria, whichever occurs first.

      Additionally, patients benefiting clinically at 1 year may continue treatment after a case by
      case review with the Sponsor.
    

Trial Arms

NameTypeDescriptionInterventions
Camidanlumab TesirineExperimentalCamidanlumab Tesirine is administered as a 30- minute intravenous (IV) infusion on Day 1 of each cycle (every 3 weeks). Camidanlumab Tesirine will be administered at a dose of 45 μg/kg every 3 weeks for 2 cycles, then 30 μg/kg for subsequent cycles.
  • Camidanlumab Tesirine

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent must be obtained prior to any procedures.

          2. Male or female participant aged 18 years or older. (16 years or older at US based
             sites)

          3. Pathologic diagnosis of classical Hodgkin lymphoma (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.

          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: Any biopsy since initial diagnosis is acceptable, but if several samples are
             available, the most recent sample is preferred.

          7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          8. Adequate organ function as defined by screening laboratory values within the following
             parameters:

               1. Absolute neutrophil count (ANC) ≥ 1.0 × 103/μL (off growth factors at least 72
                  h).

               2. Platelet count ≥ 75 × 103/μL without transfusion in the past 2 weeks.

               3. 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.

               4. Total bilirubin ≤ 1.5 × ULN (participants with known Gilbert's syndrome may have
                  a total bilirubin up to ≤ 3 × ULN with direct bilirubin ≤ 1.5 × ULN).

               5. Blood creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 60 mL/min by
                  the Cockcroft-Gault equation.

          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 16 weeks after
             the last dose of Camidanlumab Tesirine. Men with female partners who are of
             childbearing potential must agree to use a highly effective method of contraception
             from the time of giving informed consent until at least 16 weeks after the
             participants receives his last dose of Camidanlumab Tesirine.

        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 transplant 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-transplantation 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
             I 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.

         11. Participants known to be or having been infected with human immunodeficiency (HIV)
             virus, hepatitis B virus (HBV), or hepatitis C virus (HCV), and require anti-viral
             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. Hodgkin lymphoma (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 14 days prior to start of study drug.

         20. Planned live vaccine administration after starting study drug.

         21. Congenital long QT (measure between Q wave and T wave in the electrocardiogram)
             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 participants inappropriate for study participation
             or put the participant at risk.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 3 years
Safety Issue:
Description:ORR according to the 2014 Lugano classification as determined by central review in all-treated participants.ORR will be defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Up to 3 years
Safety Issue:
Description:DOR defined as the time from the first documentation of tumor response to disease progression or death.
Measure:Complete Response (CR) Rate
Time Frame:Up to 3 years
Safety Issue:
Description:CR rate defined as the percentage of treated participants with a best overall response (BOR) of CR.
Measure:Relapse-Free Survival (RFS)
Time Frame:Up to 3 years
Safety Issue:
Description:Relapse-free survival (RFS) defined as the time from the documentation of CR to disease progression or death due to any case.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:OS defined as the time from first dose of study drug until death due to any cause.
Measure:Fraction of Participants Who Receive Hematopoietic Stem Cell Transplant (HSCT)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Number of Participants Who Experience At Least One Treatment-Emergent Adverse Event (TEAE)
Time Frame:Day 1 (post-dose) until 30 days after last dose of study drug
Safety Issue:
Description:An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation where participants are administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy/procedure, whichever comes earlier.
Measure:Number of Participants Who Experience At Least One Serious Adverse Event (SAE)
Time Frame:Day 1 (post-dose) until 30 days after last dose of study drug
Safety Issue:
Description:An SAE is defined as any adverse event (AE) that: results in death. is life threatening. requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE). results in persistent or significant disability/incapacity. is a congenital anomaly/birth defect. important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.
Measure:Number of Participants Who Experience a Clinically Significant Change From Baseline in Clinical Laboratory Results
Time Frame:Day 1 to end of treatment (maximum 30 days after last dose of study drug)
Safety Issue:
Description:Parameters measured will include clinical hematology, coagulation panel, biochemistry, and urinalysis.
Measure:Number of Participants Who Experience a Clinically Significant Change From Baseline in Vital Sign Measurements
Time Frame:Day 1 to end of treatment (maximum 30 days after last dose of study drug)
Safety Issue:
Description:Vital signs include the measurements of arterial blood pressure (systolic and diastolic), heart rate (HR), respiratory rate, and body temperature.
Measure:Number of Participants Who Experience a Clinically Significant Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Time Frame:Day 1 to end of treatment (maximum 30 days after last dose of study drug)
Safety Issue:
Description:The ECOG Performance Status is a scale used to asses a person's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability. The scale consists of 6 grades, ranging from 0 to 5. A grade of 0 indicates the person is fully active and able to carry on as normal, and a grade of 5 indicates death.
Measure:Number of Participants Who Experience a Clinically Significant Change From Baseline in Electrocardiogram (ECGs) Results
Time Frame:Day 1 to end of treatment (maximum 30 days after last dose of study drug)
Safety Issue:
Description:
Measure:Maximum Observed Plasma Concentration (Cmax) of Camidanlumab Tesirine Total Antibody, PBD-Conjugated Antibody, and Unconjugated Warhead SG3199
Time Frame:Cycle 1 and 2: Day 1 (pre-dose, EOI and post-dose), Day 8 and Day 15. Cycles 3 to 6: Day 1 (pre-dose and EOI). For remaining cycles: Day 1 (pre-dose) of each cycle until EOT, maximum of 30 days after the last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Time to Reach Maximum Plasma Concentration (Tmax) of Camidanlumab Tesirine Total Antibody, PBD-Conjugated Antibody, and Unconjugated Warhead SG3199
Time Frame:Cycle 1 and 2: Day 1 (pre-dose, EOI and post-dose), Day 8 and Day 15. Cycles 3 to 6: Day 1 (pre-dose and EOI). For remaining cycles: Day 1 (pre-dose) of each cycle until EOT, maximum of 30 days after the last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) For Camidanlumab Tesirine Total Antibody, PBD-Conjugated Antibody, and Unconjugated Warhead SG3199
Time Frame:Cycle 1 and 2: Day 1 (pre-dose, EOI and post-dose), Day 8 and Day 15. Cycles 3 to 6: Day 1 (pre-dose and EOI). For remaining cycles: Day 1 (pre-dose) of each cycle until EOT, maximum of 30 days after the last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Area Under the Plasma Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) For Camidanlumab Tesirine Total Antibody, PBD-Conjugated Antibody, and Unconjugated Warhead SG3199
Time Frame:Cycle 1 and 2: Day 1 (pre-dose, EOI and post-dose), Day 8 and Day 15. Cycles 3 to 6: Day 1 (pre-dose and EOI). For remaining cycles: Day 1 (pre-dose) of each cycle until EOT, maximum of 30 days after the last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) For Camidanlumab Tesirine Total Antibody, PBD-Conjugated Antibody, and Unconjugated Warhead SG3199
Time Frame:Cycle 1 and 2: Day 1 (pre-dose, EOI and post-dose), Day 8 and Day 15. Cycles 3 to 6: Day 1 (pre-dose and EOI). For remaining cycles: Day 1 (pre-dose) of each cycle until EOT, maximum of 30 days after the last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Apparent Terminal Elimination Half-Life (T1/2) For Camidanlumab Tesirine Total Antibody, PBD-Conjugated Antibody, and Unconjugated Warhead SG3199
Time Frame:Cycle 1 and 2: Day 1 (pre-dose, EOI and post-dose), Day 8 and Day 15. Cycles 3 to 6: Day 1 (pre-dose and EOI). For remaining cycles: Day 1 (pre-dose) of each cycle until EOT, maximum of 30 days after the last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Clearance (CL) For Camidanlumab Tesirine Total Antibody, PBD-Conjugated Antibody, and Unconjugated Warhead SG3199
Time Frame:Cycle 1 and 2: Day 1 (pre-dose, EOI and post-dose), Day 8 and Day 15. Cycles 3 to 6: Day 1 (pre-dose and EOI). For remaining cycles: Day 1 (pre-dose) of each cycle until EOT, maximum of 30 days after the last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Volume of Distribution (Vd) For Camidanlumab Tesirine Total Antibody, PBD-Conjugated Antibody, and Unconjugated Warhead SG3199
Time Frame:Cycle 1 and 2: Day 1 (pre-dose, EOI and post-dose), Day 8 and Day 15. Cycles 3 to 6: Day 1 (pre-dose and EOI). For remaining cycles: Day 1 (pre-dose) of each cycle until EOT, maximum of 30 days after the last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Accumulation Index (AI) For Camidanlumab Tesirine Total Antibody, PBD-Conjugated Antibody, and Unconjugated Warhead SG3199
Time Frame:Cycle 1 and 2: Day 1 (pre-dose, EOI and post-dose), Day 8 and Day 15. Cycles 3 to 6: Day 1 (pre-dose and EOI). For remaining cycles: Day 1 (pre-dose) of each cycle until EOT, maximum of 30 days after the last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:
Measure:Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Responses
Time Frame:Day 1 until end of treatment, a maximum of 30 days after last dose of study drug
Safety Issue:
Description:Measurement of Anti-drug antibodies to ADCT-301 before, during and after treatment with Camidanlumab Tesirine
Measure:Number of Participants With At Least One ADA Titer
Time Frame:Day 1 until end of treatment, a maximum of 30 days after last dose of study drug
Safety Issue:
Description:
Measure:Number of Participants With Neutralizing Antibodies To Camidanlumab Tesirine Following Treatment With Camidanlumab Tesirine
Time Frame:Day 1 until end of treatment, a maximum of 30 days after last dose of study drug
Safety Issue:
Description:
Measure:Change from Baseline in Health-Related Quality of Life (HRQoL) as Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Time Frame:Day 1 of each 21 day cycle until end of treatment, a maximum of up to 30 days after last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:The EQ-5D-5L is a tool for evaluating quality of life (QoL). The instrument consists of 2 parts: the descriptive system and the visual analog scale (VAS). The 1st part comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The participant evaluates each dimension by ticking the box next to the most appropriate level (1-5). This decision results in a 1-digit number that represents the level selected for that dimension. A high level indicates a negative rating. These digits are combined into a 5-digit number that describes the participant's health state. The 2nd part involves the participant indicating their health state on that day on a VAS (by placing an 'X'), where the endpoints are labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0). A low score indicates a negative result.
Measure:Change from Baseline in HRQoL as Measured by Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)
Time Frame:Day 1 of each 21 day cycle until end of treatment, a maximum of up to 30 days after last dose of study drug. Each cycle is 21 days.
Safety Issue:
Description:The FACT-Lym is a lymphoma-specific subscale for the Functional Assessment of Cancer Therapy (FACT) questionnaire. The questionnaire consists of 15 specific items that are used together with the core 27-item questionnaire FACT-G. The participant is asked to give each item a score of between 0-4 (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 4 = very much). A higher score indicates a worse level of QoL.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ADC Therapeutics S.A.

Trial Keywords

  • Camidanlumab Tesirine; Relapsed or Refractory Hodgkins Lymphoma; Classical Hodgkins Lymphoma; Lymphoma

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