ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03684694
Previous Study | Return to List | Next Study

Safety and Antitumor Activity Study of Loncastuximab Tesirine + Ibrutinib in Diffuse Large B-Cell or Mantle Cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03684694
Recruitment Status : Not yet recruiting
First Posted : September 26, 2018
Last Update Posted : November 19, 2018
Sponsor:
Information provided by (Responsible Party):
ADC Therapeutics S.A.

Brief Summary:
The purpose of this Phase 1 study is to evaluate the safety and antitumor activity of Loncastuximab Tesirine (ADCT-402) and Ibrutinib in patients with Advanced Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma.

Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Mantle Cell Lymphoma Drug: Loncastuximab Tesirine and Ibrutinib Phase 1

Detailed Description:

This is a Phase 1b, open-label, single-arm combination study with a dose escalation phase (Part 1) followed by a dose expansion phase (Part 2). The study will enroll approximately 60 patients.

A standard 3+3 dose escalation design will be used for Part 1. The DLT period will be the 21 days following the first dose of ibrutinib. The initial dose escalation cohort will receive loncastuximab tesirine for 2 cycles with concurrent ibrutinib (concomitant therapy) and may then continue ibrutinib therapy up to one year. Depending on the safety and tolerability of loncastuximab tesirine given concurrently with ibrutinib in the initial cohort, subsequent cohorts may receive either loncastuximab tesirine with concurrent ibrutinib or loncastuximab tesirine followed by ibrutinib (sequential therapy).

Patients who have a response of PR or stable disease (SD) at the 14-week assessment may receive two additional doses of loncastuximab tesirine given 4 weeks apart.

Part 2 will consist of up to two expansion cohorts, one for DLBCL and one for MCL. Each cohort will be 20 patients treated at the dose determined in Part 1.

The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3 to 4 weeks), and a Follow-up Period (approximately every 12 week visits for up to 2 years after treatment discontinuation).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Open-Label Study to Evaluate the Safety and Antitumor Activity of Loncastuximab Tesirine and Ibrutinib in Patients With Advanced Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : September 2022


Arm Intervention/treatment
Experimental: ADCT-402
A standard 3+3 dose escalation design will be used. The DLT period will be the 21 days following the first dose of ibrutinib. The initial dose escalation cohort will receive loncastuximab tesirine for 2 cycles with concurrent ibrutinib (concomitant therapy) and may then continue ibrutinib therapy up to one year. Depending on the safety and tolerability of loncastuximab tesirine given concurrently with ibrutinib in the initial cohort, subsequent cohorts may receive either loncastuximab tesirine with concurrent ibrutinib or loncastuximab tesirine followed by ibrutinib (sequential therapy).
Drug: Loncastuximab Tesirine and Ibrutinib
oral
Other Name: ADCT-402 in combination with ibrutinib




Primary Outcome Measures :
  1. Safety and tolerability of loncastuximab tesirine in combination with ibrutinib by measuring frequency and severity of adverse events (AEs) [ Time Frame: Until 30 days after last dose ]
  2. Safety and tolerability of loncastuximab tesirine in combination with ibrutinib by measuring frequency and severity of serious adverse events (SAEs) [ Time Frame: Until 30 days after last dose ]
  3. Safety and tolerability of loncastuximab tesirine in combination with ibrutinib by measuring incidence of dose limiting toxicities (DLTs) (dose escalation only) [ Time Frame: First 21-day cycle for each patient (dose escalation only) ]

Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Up to 2 years ]
    ORR according to the 2014 Lugano classification, defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR)

  2. Complete Response Rate (CR) [ Time Frame: Up to 2 years ]
    CR rate defined as the percentage of treated patients with a BOR of CR

  3. Duration of Response (DOR): time from first tumor response to disease progression or death [ Time Frame: Up to 2 years ]
  4. Overall survival (time between the start of treatment and death from any cause) [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patient aged 18 years or older
  2. Pathologic diagnosis of DLBCL, non-GCB subtype; or MCL
  3. Patients with DLBCL must have relapsed or refractory disease and have failed or been intolerant to available standard therapy
  4. Patients with MCL must have relapsed or refractory disease and have received at least one prior line of therapy
  5. Patients who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy
  6. Measurable disease as defined by the 2014 Lugano Classification
  7. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available)
  8. ECOG performance status 0 to 2
  9. Screening laboratory values within the following parameters:

    1. Absolute neutrophil count (ANC) ≥1.0 × 103/µL (off growth factors at least 72 hours)
    2. Platelet count ≥75 × 103/µL without transfusion in the past 7 days
    3. Hemoglobin ≥8 g/dL (4.96 mmol/L), transfusion allowed
    4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 × the upper limit of normal (ULN); ≤5 × ULN if there is liver involvement
    5. Total bilirubin ≤1.5 × ULN (patients with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN)
    6. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft and Gault equation
  10. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drugs on C1D1 for women of childbearing potential
  11. Women of childbearing potential* must agree to use a highly effective** method of contraception from the time of giving informed consent until at least 16 weeks after the last dose of study therapy. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the patient receives his last dose of study therapy

Exclusion Criteria:

  1. Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody
  2. Known history of hypersensitivity to ibrutinib
  3. Previous therapy with ibrutinib or other BTK inhibitors
  4. Previous therapy with loncastuximab tesirine
  5. Requires treatment or prophylaxis with a moderate or strong cytochrome P450 (CYP) 3A inhibitor
  6. Allogenic or autologous transplant within 60 days prior to start of study drugs (C1D1)
  7. Active graft-versus-host disease
  8. Post-transplantation lymphoproliferative disorder
  9. Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
  10. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). Note: Testing is not mandatory to be eligible
  11. History of Stevens-Johnson syndrome or toxic epidermal necrolysis
  12. Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease
  13. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
  14. Breastfeeding or pregnant
  15. Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure [BP] ≥160/100 mmHg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes mellitus, or severe chronic pulmonary disease
  16. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drugs (C1D1), except shorter if approved by the Sponsor
  17. Use of any other experimental medication within 14 days prior to start of study drugs (C1D1)
  18. Planned live vaccine administration after starting study drugs (C1D1)
  19. Any condition that could interfere with the absorption or metabolism of ibrutinib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
  20. Inherited or acquired bleeding disorders
  21. Ongoing anticoagulation with warfarin or equivalent vitamin K antagonists
  22. Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) from acute non-hematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening
  23. Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block)
  24. 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 that the Sponsor's medical monitor and Investigator agree, and document should not be exclusionary
  25. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03684694


Contacts
Contact: ADC Therapeutics 954-903-7994 clinical.trials@adctherapeutics.com

Sponsors and Collaborators
ADC Therapeutics S.A.

Responsible Party: ADC Therapeutics S.A.
ClinicalTrials.gov Identifier: NCT03684694     History of Changes
Other Study ID Numbers: ADCT-402-103
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: November 19, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ADC Therapeutics S.A.:
Loncastuximab Tesirine in Combination with Ibrutinib

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin