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Trial record 1 of 1 for:    NCT03685344
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Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in Diffuse Large B-Cell, Mantle Cell, or Follicular 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03685344
Recruitment Status : Active, not recruiting
First Posted : September 26, 2018
Last Update Posted : July 15, 2020
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 anti-tumor activity of Loncastuximab Tesirine (ADCT-402) and Durvalumab in participants with Advanced Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma

Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Mantle Cell Lymphoma Follicular Lymphoma Drug: Loncastuximab Tesirine and Durvalumab 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 75 participants.

A standard 3+3 dose escalation design will be used for Part 1. The DLT period will be the 21 days after the first durvalumab dose.

Part 2 will consist of up to 3 expansion cohorts, one for DLBCL, one for MCL, and one for FL. Each cohort will be approximately 20 participants 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, 6, and 4 weeks), and a Follow-up Period (approximately every 12 week visits for up to 2 years after treatment discontinuation).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label Study to Evaluate the Safety and Antitumor Activity of Loncastuximab Tesirine and Durvalumab in Patients With Advanced Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma
Actual Study Start Date : December 6, 2018
Estimated Primary Completion Date : January 29, 2021
Estimated Study Completion Date : January 29, 2021


Arm Intervention/treatment
Experimental: ADCT-402

Dose escalation phase: Ascending doses of Loncastuximab tesirine will be administered using a traditional 3+3 design. Dose level 1: 90 µg/kg, every 3 weeks (Q3W). Dose level 2: 120 µg/kg, Q3W. Dose level 3: 150 µg/kg, Q3W. Loncastuximab tesirine will be given for 2 doses, 3 weeks apart.

Dose expansion phase: Loncastuximab tesirine will be administered at the recommended dose determined in the dose escalation phase. Durvalumab will also be administered at a dose of 1500 mg once every 4 weeks (Q4W) throughout the dose escalation phase and dose expansion phase.

Drug: Loncastuximab Tesirine and Durvalumab
intravenous infusion
Other Name: ADCT-402 in combination with Durvalumab




Primary Outcome Measures :
  1. Number of Adverse Events (AEs) [ Time Frame: Day 1 until 30 days after the last dose of study drug ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product, which does not necessarily have to have a casual relationship with this treatment.

  2. Number of Adverse Events of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Day 1 until 30 days after last dose of study drug ]
    Adverse events will be graded according to CTAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.

  3. Number of Serious Adverse Events (SAE) [ Time Frame: Day 1 to the end of follow-up period; maximum length of follow up is 2 years ]
    A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization of prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the patient or may require medical or surgical intervention to prevent any of the outcomes listed above.

  4. Number of SAEs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Day 1 to the end of follow-up period; maximum length of follow up is 2 years ]
    AEs will be graded according to CTCAE v.4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.

  5. Number of dose limiting toxicities (DLTs) (dose escalation only) [ Time Frame: First 21-day cycle for each patient (dose escalation only) ]
  6. Number of Participants who Experience a Clinically Significant Change in Baseline in Laboratory Values [ Time Frame: Day 1 to end of trial; maximum of 3 years ]
  7. Number of Participants who Experience a Clinically Significant Change in Baseline in Vital Signs [ Time Frame: Day 1 to end of trial; maximum of 3 years ]
  8. Number of Participants who Experience a Clinically Significant Change in Baseline in Electrocardiogram (ECG) Results [ Time Frame: Day 1 to end of trial; maximum of 3 years ]
  9. Number of Particpants who Experience a Clinically Significant Change in Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Day 1 to end of trial; maximum of 3 years ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
    ORR according to the 2014 Lugano classification, defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR)

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

  3. Duration of response (DOR) [ Time Frame: Up to 3 years ]
    Time from first tumor response to disease progression or death

  4. Overall survival (OS) [ Time Frame: Up to 2 years ]
    Time between the start of treatment and death from any cause

  5. Relapse-Free Survival (RFS) [ Time Frame: Up to 2 years ]
    Time from the documentation of CR to disease progression or death

  6. Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]
    Time between start of treatment and the first documentation of progression, or death

  7. Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine [ Time Frame: Cycle 3, Cycle 5, Cycle 6, and Cycle 7 (each cycle is 28 days) ]
  8. Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine [ Time Frame: Cycle 3, Cycle 5, Cycle 6, and Cycle 7 (each cycle is 28 days) ]
  9. Area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0 last) [ Time Frame: Cycle 3, Cycle 5, Cycle 6, and Cycle 7 (each cycle is 28 days) ]


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.


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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 participants aged 18 years or older
  2. Pathologic diagnosis of DLBCL, MCL, or FL
  3. Participants must have relapsed or refractory disease and have failed or been intolerant to standard therapy
  4. Participants who have received previous CD19-directed therapy must have a biopsy that shows CD19 expression after completion of the CD19-directed therapy
  5. Measurable disease as defined by the 2014 Lugano Classification
  6. Participants must be willing to undergo tumor biopsy
  7. ECOG performance status 0-1
  8. 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 ≥9.0 g/dL (5.59 mmol/L), transfusion allowed
    4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and GGT ≤2.5 × the upper limit of normal (ULN)
    5. Total bilirubin ≤1.5 × ULN (participants 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-Gault equation
  9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 3 days prior to start of study drug on C1D1 for women of childbearing potential
  10. 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. Previous therapy with any checkpoint inhibitor
  3. Autologous stem cell transplant within 100 days prior to start of study drug (C1D1)
  4. History of allogenic stem cell transplant
  5. History of solid organ transplant
  6. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:

    1. Participants with vitiligo or alopecia
    2. Participants with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
    3. Any chronic skin condition that does not require systemic therapy
    4. Participants without active disease in the last 5 years may be included but only after consultation with the Study Physician
    5. Participants with celiac disease controlled by diet alone
  7. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice)
  8. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV)
  9. History of Stevens-Johnson syndrome or toxic epidermal necrolysis
  10. Lymphoma with active central nervous system (CNS) involvement at the time of screening, including leptomeningeal disease
  11. 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)
  12. Breastfeeding or pregnant
  13. 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, or severe chronic pulmonary disease
  14. Radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor.
  15. Major surgery within 28 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  16. Use of any other experimental medication within 14 days prior to start of study drug (C1D1)
  17. Planned live vaccine administration after starting study drug (C1D1)
  18. 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.
  19. Congenital long QT syndrome or a corrected QTcF interval of >470 ms at screening (unless secondary to pacemaker or bundle branch block)
  20. History of another primary malignancy except for:

    1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product and of low potential risk for recurrence
    2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    3. Adequately treated carcinoma in situ without evidence of disease 21. History of active primary immunodeficiency
  21. History of active primary immunodeficiency or any other significant medical illness, abnormality, or condition that would, in the Investigator's judgement, make the patient inappropriate for study participation or put the participant 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): NCT03685344


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Colorado
UCH-MHS Memorial Hospital Centeral
Colorado Springs, Colorado, United States, 80909
United States, Florida
University of Florida Health Shands Cancer Hospital
Gainesville, Florida, United States, 32603
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, New York
Icahm School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, United States, 79410
Baylor Scott & White Medical Center - Temple
Temple, Texas, United States, 76508
Spain
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital General Universitario Gregorio Marañon Pabellón de Oncología
Madrid, Spain, 28009
Hospital Universitario Fundación Jiménez Díaz Unidad de Limfomas Servicio de Hematologia
Madrid, Spain, 28040
Hospital Universitario Virgen Macarena Servicio Oncologia Medica
Sevilla, Spain, 41009
Hospital Universitario Virgen Del Rocio
Sevilla, Spain, 41015
Sponsors and Collaborators
ADC Therapeutics S.A.
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Responsible Party: ADC Therapeutics S.A.
ClinicalTrials.gov Identifier: NCT03685344    
Other Study ID Numbers: ADCT-402-104
2018-002670-43 ( EudraCT Number )
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: July 15, 2020
Last Verified: July 2020

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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 Durvalumab
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
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
Durvalumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs