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Trial record 1 of 1 for:    Study NCT02432235
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Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by ADC Therapeutics SARL
Sponsor:
Information provided by (Responsible Party):
ADC Therapeutics SARL
ClinicalTrials.gov Identifier:
NCT02432235
First received: February 26, 2015
Last updated: April 27, 2017
Last verified: April 2017
  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 of ADCT-301 every 3 weeks.


Condition Intervention Phase
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 Drug: ADCT-301 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by ADC Therapeutics SARL:

Primary Outcome Measures:
  • Assessment of Dose Limiting Toxicities in Determination of the Maximum Tolerated Dose [ Time Frame: The protocol-defined assessment period is 1 21-day cycle ]
    Dose Limiting toxicities as defined per protocol, as related to ADCT-301


Secondary Outcome Measures:
  • 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. ]
    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

  • 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. ]
    Noncompartmental analysis of the maximum concentration (Cmax)

  • 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. ]
    Noncompartmental analysis of the time to maximum concentration (Tmax)

  • 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. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0 last)

  • 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. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ)

  • 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. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to infinity (AUC0-∞)

  • 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. ]
    Noncompartmental analysis of the accumulation index (AI)

  • 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. ]
    Noncompartmental analysis of the volume of distribution at a steady-state (Vss)

  • 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. ]
    Noncompartmental analysis of the mean residence time (MRT)

  • 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. ]
    Noncompartmental analysis of the terminal elimination phase rate constant (λz)

  • 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. ]
    Noncompartmental analysis of T1/2

  • 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. ]
    Noncompartmental analysis of CL

  • 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. ]
    Noncompartmental analysis of Vz

  • 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 ]
    Expressed as either negative or positive titer expressed as a dilution factor


Estimated Enrollment: 90
Study Start Date: June 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ADCT-301

In Part 1 (dose-escalation), patients will receive a 2-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 of ADCT-301 as determined by the Dose Escalation Steering Committee (DESC).

Drug: ADCT-301
intravenous infusion

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 30 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 a recommended dose 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
  4. Known history of positive serum human anti-drug antibody (ADA), or known allergy to any component of ADCT-301
  5. History of symptomatic autoimmune disease
  6. Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV)
  7. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
  8. Pregnant or breastfeeding women.
  9. 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.
  10. Use of any other experimental medication(s) within 14 days prior to start of the study treatment.
  11. Steroid use equivalent to greater than 20 mg of prednisone within 4 weeks prior to Day 1
  12. Major surgery, chemotherapy, systemic therapy (excluding steroids and including any targeted small molecules or biologics), or radiotherapy within 14 days prior to 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02432235

Contacts
Contact: Maria Cincotta Maria.Cincotta@adctherapeutics.com
Contact: Jay Feingold Jay.Feingold@adctherapeutics.com

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Principal Investigator: Steven Horwitz, MD         
United States, Texas
The University of Texas/MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030-4009
Principal Investigator: Michelle A Fanale, MD         
Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Anand Karnad, MD         
United States, Virginia
Virginia Cancer Specialists, PC Recruiting
Fairfax, Virginia, United States, 22031
Principal Investigator: Alexander Spira, MD, PhD         
United States, Wisconsin
Froedtert Hospital/Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Principal Investigator: Mehdi Hamadani, MD         
United Kingdom
Guy's and St. Thomas' Hospital NHS Trust Recruiting
London, England, United Kingdom, SE1 9RT
Principal Investigator: Paul A Fields, MBchB         
The Newcastle Upon Tyne Hospitals NHS Foundation Trust Recruiting
Newcastle upon Tyne, England, United Kingdom
Principal Investigator: Tobias F Menne, MD         
Churchill Hospital, Oxford University Hospitals NHS Foundation Trust Recruiting
Oxford, England, United Kingdom, OX3 7LE
Principal Investigator: Graham P Collins, MBBS         
Southampton General Hospital, University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, Hampshire, United Kingdom
Principal Investigator: Andrew J Davies, MBBS         
Sponsors and Collaborators
ADC Therapeutics SARL
  More Information

Responsible Party: ADC Therapeutics SARL
ClinicalTrials.gov Identifier: NCT02432235     History of Changes
Other Study ID Numbers: ADCT-301-001
Study First Received: February 26, 2015
Last Updated: April 27, 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Burkitt Lymphoma
Waldenstrom Macroglobulinemia
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Follicular
Lymphoma, T-Cell
Lymphoma, Mantle-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, B-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 19, 2017