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

NCT02669264 | Terminated Phase 1 Results

• 1 other identifier: ADCT-402-102
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 10

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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Loncastuximab tesirine

Outcome Measures

Primary Outcomes (4)

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as: \- Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with \<5% blasts). In case of a normocellular bone marrow with \<5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT. A non-hematologic DLT is defined as: * Grade 4 tumor lysis syndrome (Grade 3 TLS will not constitute DLT unless it leads to irreversible end-organ damage). * Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). * CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). * CTCAE Grade 3 or higher skin ulceration.

  Day 1 to End of Cycle 1 (3 weeks)

• Recommended Dose of ADCT-402 for Part 2

  The recommended dose was to be established by the dose escalation steering committee and based on safety findings during part 1 of the study.

  Day 1 to End of Cycle 1 (3 weeks)

• Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)

  An adverse event (AE) is defined as any untoward medical occurrence in a participants enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.

  From first dose of study drug up to 12 weeks after last dose (up to 39 weeks)

• Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)

  An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

  From first dose of study drug up to 12 weeks after last dose (up to 39 weeks)

Secondary Outcomes (26)

• Overall Response Rate (ORR)

  From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug

• Duration of Response

  From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug

• Overall Survival

  From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug

• Progression-free Survival

  From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug

• Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W)

  Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2

Study Arms (2)

Part 1: ADCT-402 dose escalation

EXPERIMENTAL

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.

Drug: ADCT-402

Part 2: ADCT-402 expansion

EXPERIMENTAL

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

Drug: ADCT-402

Interventions

ADCT-402 DRUG

Intravenous infusion

Also known as: Loncastuximab tesirine, Zynlonta

Part 1: ADCT-402 dose escalation; Part 2: ADCT-402 expansion

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (10)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06510, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University Hospital of Cleveland

Cleveland, Ohio, 44106, United States

Location

The Ohio State University Wexner Medical Center, James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 32012214 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

loncastuximab tesirine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The study was early terminated prior to part 2 because of slow accrual. Formal assessment of potential anti-leukemic effect was not undertaken because of the early termination of the study.

Results Point of Contact

• Title: ADC Therapeutics
• Organization: ADC Therapeutics

clinical.trials@adctherapeutics.com

954-903-7994

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: February 1, 2016
• Study Start: March 1, 2016
• Primary Completion: July 3, 2018
• Study Completion: July 3, 2018
• Last Updated: May 24, 2021
• Results First Posted: September 26, 2019

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)