Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Acute Lymphoblastic Leukemia (B-ALL)

NCT ID: NCT02669264

Last Updated: 2021-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2018-07-03

Brief Summary

This study evaluates ADCT-402 in participants with relapsed or refractory B-cell lineage acute lymphoblastic leukemia (B-ALL). Participants will participate in a dose-escalation phase (Part 1) and dose expansion (Part 2). In Part 2, participants will receive the dose level identified in Part 1.

Detailed Description

Study ADCT-402-102 is the first clinical study with ADCT-402 in participants with B-cell lineage acute lymphoblastic leukemia (B-ALL).

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) participants will receive an infusion of ADCT-402 either on weekly administration or every 3-week administration. participants on weekly administration will receive an infusion of ADCT-402 on Days 1, 8, and 15 of each 3 week treatment cycle. Participants on 3-week administration will receive an infusion of ADCT-402 on Day 1, every 3 weeks. Dose escalation will continue until the maximum tolerated dose (MTD) is determined.

In Part 2 (expansion), all participants will be assigned to the recommended dose and/or schedule 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.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: ADCT-402 dose escalation

Weekly administration - Participants will receive an intravenous (IV) infusion of ADCT-402, on Days 1, 8, and 15 of each 3-week (21-day) cycle.

3-week administration - Participants will receive an IV infusion of ADCT-402, on Day 1 of each 3-week (21-day) cycle.

The dose escalation will be conducted according to a 3+3 design.

Group Type: EXPERIMENTAL

ADCT-402

Intervention Type: DRUG

Intravenous infusion

Part 2: ADCT-402 expansion

All participants will be assigned to the recommended dose and/or schedule of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee

Group Type: EXPERIMENTAL

ADCT-402

Intervention Type: DRUG

Intravenous infusion

Interventions

ADCT-402

Intravenous infusion

Intervention Type: DRUG

Other Intervention Names

Loncastuximab tesirine; Zynlonta

Eligibility Criteria

Inclusion Criteria

• Male or female patients, ages 12 years and older, with relapsed or refractory B-ALL who have failed, or are intolerant to, any established therapy; or for whom no other treatment options are available.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Serum/plasma creatinine ≤1.5mg/dL.
• Serum/plasma 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.
• White Blood Cell Count value of <15,000 cells/μL prior to Cycle 1 Day 1.
• Negative urine or serum beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to the Cycle 1, Day 1 visit, 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.

Exclusion Criteria

• Patients who have an option for other treatment for B-ALL at the current state of disease.
• Known active central nervous system (CNS) leukemia.
• Patients with Burkitt's leukemia/lymphoma.
• Active graft-versus-host disease.
• Autologous or allogenic transplant within the 60 days prior to Screening.
• Known history of immunogenicity or hypersensitivity to a CD19 antibody.
• Known history of positive serum human ADA.
• Active autoimmune disease, motor neuropathy considered of autoimmune origin, or other central nervous system autoimmune disease.
• Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV).
• History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome.
• Pregnant or breastfeeding women.
• Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure >115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, 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 <14 days prior to the start of treatment on Cycle 1, Day 1, except if approved by the Sponsor.
• Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea,steroids and any targeted small molecules or biologics), or radiotherapy, within 14 days or 5 half-lives (whichever is shorter) prior to the Cycle 1, Day 1 treatment, except if approved by the Sponsor.
• Failure to recover from acute non hematologic toxicity (except alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening.
• Isolated extramedullary relapse.
• Congenital long QT syndrome or a corrected QTc interval of ≥450 ms at the Screening visit.
• 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 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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADC Therapeutics S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UC San Diego Moores Cancer Center

La Jolla, California, United States

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, United States

Emory University Hospital

Atlanta, Georgia, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

University Hospital of Cleveland

Cleveland, Ohio, United States

The Ohio State University Wexner Medical Center, James Cancer Hospital

Columbus, Ohio, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Jain N, Stock W, Zeidan A, Atallah E, McCloskey J, Heffner L, Tomlinson B, Bhatnagar B, Feingold J, Ungar D, Chao G, Zhang X, Qin Y, Havenith K, Kantarjian H, Wieduwilt MJ. Loncastuximab tesirine, an anti-CD19 antibody-drug conjugate, in relapsed/refractory B-cell acute lymphoblastic leukemia. Blood Adv. 2020 Feb 11;4(3):449-457. doi: 10.1182/bloodadvances.2019000767.

Reference Type: DERIVED

PMID: 32012214 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ADCT-402-102

Identifier Type: -

Identifier Source: org_study_id