Clinical Trials /

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

NCT02432235

Description:

This study evaluates ADCT-301 in patients with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma. Patients will participate in a dose-escalation phase (Part 1) and receive escalating doses of ADCT-301 every 3 weeks. In Part 2 of the study, patients will receive a recommended dose(s) of ADCT-301 every 3 weeks.

Related Conditions:
  • Lymphoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ADCT-301-001
  • NCT ID: NCT02432235

Conditions

  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
  • Burkitt's Lymphoma
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Follicular
  • Lymphoma, Mantle-Cell
  • Lymphoma, Marginal Zone
  • Waldenstrom's Macroglobulinaemia
  • Lymphoma,T-cell Cutaneous
  • Lymphoma, T-Cell, Peripheral

Interventions

DrugSynonymsArms
ADCT-301Camidanlumab tesirineADCT-301

Purpose

This study evaluates ADCT-301 in patients with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma. Patients will participate in a dose-escalation phase (Part 1) and receive escalating doses of ADCT-301 every 3 weeks. In Part 2 of the study, patients will receive a recommended dose(s) of ADCT-301 every 3 weeks.

Detailed Description

      This is a Phase I, first in human clinical study with ADCT-301 to evaluate the safety and
      tolerability and pharmacokinetics of ADCT-301 in patients with relapsed/refractory lymphoma.

      ADCT-301 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: In part 1 (dose escalation) up to 80 patients will
      receive an infusion of ADCT-301 on Day 1, every 3 weeks. Dose escalation will continue until
      the maximum tolerated dose (MTD) is determined.

      In Part 2 (expansion) up to 60 patients will be assigned to receive the recommended dose(s)
      of ADCT-301 as determined by a Dose Escalation Steering Committee.

      For each patient, the study will include a screening period (up to 28 days), a treatment
      period, and a follow-up period to assess disease progression and survival for up to 12 months
      after the last dose of study drug. The total study duration will be dependent on overall
      patient tolerability to the study drug and response to treatment. It is anticipated that the
      entire study (Parts 1 and 2) could last approximately 3 years from first patient treated to
      last patient completed.
    

Trial Arms

NameTypeDescriptionInterventions
ADCT-301ExperimentalIn Part 1 (dose-escalation), patients will receive a 1-hour intravenous infusion of ADCT-301 on Day 1 every 3 weeks (21-day cycle). Dose escalation will be conducted according to a continual reassessment method. In Part 2 (expansion), patients will be assigned to receive the recommended dose(s) of ADCT-301 as determined by the Dose Escalation Steering Committee (DESC).
  • ADCT-301

Eligibility Criteria

        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

          6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

          7. Absolute neutrophil count ≥1500/µL.

          8. Platelet count of ≥75000/µL.

          9. Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.

         10. Creatinine ≤1.5mg/dL

         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 bilirubin ≤1.5 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. Patients 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.

          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

          7. Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen
             (HbsAg), or antibody to hepatitis C virus (anti-HCV)

          8. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.

          9. Pregnant or breastfeeding women.

         10. Significant medical comorbidities, including uncontrolled hypertension (diastolic
             blood pressure greater than 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.

         11. Use of any other experimental medication(s) within 14 days prior to start of the study
             treatment.

         12. 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.

         13. 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 alopecia or Grade
             2 or lower neuropathy), due to previous therapy, prior to Screening.

         14. Congenital long QT syndrome or a corrected QTc interval ≥ 470 ms at screening

         15. 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

         16. Any other significant medical illness, abnormality, or condition
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of Dose Limiting Toxicities in Determination of the Maximum Tolerated Dose
Time Frame:The protocol-defined assessment period is 1 21-day cycle
Safety Issue:
Description:Dose Limiting toxicities as defined per protocol, as related to ADCT-301

Secondary Outcome Measures

Measure:Overall Response Rate, Duration of Response, Progression Free Survival, and Overall Survival (composite endpoint)
Time Frame:Disease assessments will occur within 6 days prior to Day 1 of Cycles 3 and 5 and thereafter every third cycle until progression of disease or initiation of a new anticancer therapy for up to 12 months.
Safety Issue:
Description:Date of disease progression will be defined as the earliest date of radiological disease progression as assessed by the investigator using the 2014 Lugano Classification for response for Hodgkin and Non-Hodgkin Lymphoma or Global Response Score criteria for disease progression
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of the maximum concentration (Cmax)
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of the time to maximum concentration (Tmax)
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of the area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0 last)
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of the area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ)
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of the area under the concentration-time curve from time zero to infinity (AUC0-∞)
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of the accumulation index (AI)
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of the volume of distribution at a steady-state (Vss)
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of the mean residence time (MRT)
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of the terminal elimination phase rate constant (λz)
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of T1/2
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of CL
Measure:Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199
Time Frame:Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2.
Safety Issue:
Description:Noncompartmental analysis of Vz
Measure:Evaluation of anti-drug antibodies (ADAs) in blood before, during, and after treatment with ADCT 301
Time Frame:Blood sample collection on Day 1 of each 21 day cycle
Safety Issue:
Description:Expressed as either negative or positive titer expressed as a dilution factor

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:ADC Therapeutics S.A.

Trial Keywords

  • Camidanlumab tesirine

Last Updated

December 3, 2019