Summary

for people ages 18 years and up (full criteria)
at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

This study evaluates ADCT-402 in patients with Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL). Patients will participate in a dose-escalation phase (Part 1) and dose expansion (Part 2). In Part 2, patients will receive the dose level identified in Part 1.

Official Title

A Phase 1 Dose-escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)

Details

Study ADCT-402-101 is the first clinical study with ADCT-402 in patients with B-cell non-Hodgkin Lymphoma (NHL).

ADCT-402 is an antibody drug conjugate (ADC) composed of a humanized antibody directed against human cluster of differentiation 19 (CD19), stochastically conjugated via a valine-alanine cleavable, maleimide linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin.

The study will be conducted in 2 parts. In Part 1 (dose escalation) patients will receive an infusion of ADCT-402, at escalating doses. Part 1 will continue until the maximum tolerated dose is determined. In Part 2 (expansion), patients will be assigned to the recommended dose level(s) and schedule(s) of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee.

For each patient, the study will include a screening period (up to 28 days), a treatment period (until withdrawal), 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 duration of the entire study (Parts 1 and 2) could be approximately 3 years from first patient treated to last patient completed.

Keywords

Non-Hodgkin Lymphoma Burkitt's Lymphoma Chronic Lymphocytic Leukemia Lymphoma, Large B-Cell, Diffuse Lymphoma, Follicular Lymphoma, Mantle-Cell Lymphoma, Marginal Zone Waldenstrom Macroglobulinemia Loncastuximab tesirine Lymphoma Lymphoma, Non-Hodgkin Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Burkitt Lymphoma ADCT-402

Eligibility

You can join if…

Open to people ages 18 years and up

  • Male or female patients, ages 18 years or older with pathologically confirmed relapsed or refractory B-cell lineage NHL who have failed or are intolerant to established therapy, or for whom no other treatment options are available. Refractory or relapsed B-cell NHL (per World health Organization [WHO] Classification system)
  • Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
  • Measurable disease, as defined by the 2014 Lugano Classification.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
  • Absolute neutrophil count (ANC) ≥1000/μL.
  • Platelet count of ≥75000/μL.
  • Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.
  • Serum/plasma creatinine ≤1.5 mg/dL.
  • Serum/plasma alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2 times the upper limit of normal (ULN); ≤ 5 times ULN if there is liver or bone involvement.
  • Total serum/plasma bilirubin ≤1.5 times ULN.
  • Negative blood or urine beta-human chorionic gonadotropin (β- HCG) pregnancy test within 7 days prior to Day 1 for women of childbearing potential.
  • Males, and female patients who are biologically capable of having children, must agree to use a medically acceptable method of birth control.

You CAN'T join if...

  • Patients who have any option for other treatment for B-cell NHL at the current state of disease.
  • Active graft-versus-host disease.
  • Autologous or allogenic transplant within the 60 days prior to the Screening visit.
  • Known history of immunogenicity or hypersensitivity to a CD19 antibody.
  • Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
  • Known history of positive serum human ADA.
  • Active autoimmune disease, motor neuropathy considered of autoimmune origin, and other central nervous system (CNS) autoimmune disease.
  • Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen(HbsAg), or antibody to hepatitis C virus (anti-HCV).
  • History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
  • Pregnant or breastfeeding women.
  • 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.
  • Use of any other experimental medication(s) within 14 days or 5 half-lives but in no case less than 14 days prior to start of study treatment on Cycle 1, Day 1, except if approved by Sponsor.
  • Steroid use equivalent to greater than 20 mg of prednisone within 4 weeks (28 days)prior to Day 1.
  • Major surgery, chemotherapy, systemic therapy (excluding steroids hydroxyurea steroids, and any targeted small molecules or biologics), or radiotherapy, within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except if approved by the Sponsor.
  • Failure to recover (to Common Terminology Criteria for Adverse Events [CTCAE] Grade 0 or Grade 1) from acute non hematologic toxicity (except all grades alopecia or Grade 2 or lower neuropathy ), due to previous therapy, prior to Screening.
  • Congenital long QT syndrome or a corrected QTc interval ≥450 ms at the Screening visit.
  • 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 determined not be exclusionary.
  • Any other significant medical illness, abnormality, or condition that would make the patient inappropriate for study participation or put the patient at risk.

Locations

  • UC San Diego Moores Cancer Center
    La Jolla California 92093 United States
  • Washington University School of Medicine
    Saint Louis Missouri 63110 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
ADC Therapeutics S.A.
ID
NCT02669017
Phase
Phase 1
Study Type
Interventional
Last Updated