AzTrials
AzTrials

Diffuse Large B-Cell LymphomaPhase 1LOTIS-8NCT04974996

A Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of Loncastuximab Tesirine in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untreated Diffuse Large B-cell Lymphoma (LOTIS-8)

A Phase 1 study testing Loncastuximab tesirine, Prednisone and Rituximab in people with Diffuse Large B-Cell Lymphoma, run by ADC Therapeutics S.A. at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

The primary objective of this study is to characterize the safety and tolerability of loncastuximab tesirine in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, and identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) for the… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-Cell Lymphoma
What is being tested?
Loncastuximab tesirine, Prednisone and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
1 Feb 2022to 5 May 2027
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent must be obtained prior to any study procedures
  • Male or female participant aged 18 years or older
  • Pathologic diagnosis of diffuse large B-cell lymphoma (DLBCL), as defined by the 2016 World Health Organization classification (including participants with DLBCL transformed from indolent lymphoma), or high-grade B cell lymphoma
  • Measurable disease as defined by the 2014 Lugano Classification
  • Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue sample. (If tissue block is not available, slides from a FFPE block may be acceptable for eligibility upon consultation with the Sponsor)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Show all 19Show fewer
  • Adequate organ function as defined by screening laboratory values within the following parameters:
  • Absolute neutrophil count ≥1.5 × 10^3/μL (off growth factors at least 72 hours)
  • Platelet count ≥75 × 10^3/μL without transfusion in the past 7 days
  • Hemoglobin ≥9 g/dL (4.96 mmol/L), transfusion allowed
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 × the upper limit of normal (ULN)
  • Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN)
  • Calculated creatinine clearance >30 mL/min by the Cockcroft and Gault equation
  • Note: A laboratory assessment may be repeated a maximum of two times during the Screening period to confirm eligibility.
  • Left ventricular ejection fraction (LVEF) of ≥50%, assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan
  • Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9 months after the last dose of study drug. Men with female partners who are of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 6 months after the last dose of study drug.
  • Women of childbearing potential are defined as sexually mature women who have not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or who have not been postmenopausal (i.e., who have not menstruated at all) for at least one year. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
  • Highly effective forms of birth control are methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Highly effective forms of birth control include: hormonal contraceptives (oral, injectable, patch, intrauterine devices), male partner sterilization, or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the participant.
  • Note: The double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, post ovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and spermicide-only are not acceptable as highly effective methods of contraception.

Who cannot join

  • Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA) to a cluster of differentiation 19 (CD19) antibody
  • Previous therapy with loncastuximab tesirine, rituximab, anthracycline, or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)
  • Known history of hypersensitivity to any component of study treatment (loncastuximab tesirine and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP])
  • Previous treatment for aggressive lymphoma (with exception of short corticosteroid course [up to 7 days] for symptom management)
  • Contraindication to receive granulocyte colony stimulating factors
  • Human immunodeficiency virus (HIV) seropositive with any of the following:
Show all 24Show fewer
  • Cluster of differentiation 4 (CD4) + T-cell (CD4+) counts <350 cells/μL
  • Acquired immunodeficiency syndrome-defining opportunistic infection within 12 months prior to screening
  • Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the time of Screening
  • HIV viral load ≥400 copies/mL
  • Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load
  • Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
  • History of Stevens-Johnson syndrome or toxic epidermal necrolysis
  • Lymphoma with active central nervous system involvement at the time of Screening, including leptomeningeal disease
  • 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)
  • Breastfeeding or pregnant
  • 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.
  • Active systemic bacterial, viral, fungal, or other infection requiring systemic treatment at the time of Screening
  • Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (Cycle 1 Day 1 [C1D1]; cycle is 21 days), except shorter if approved by the Sponsor
  • Use of any other experimental medication within 14 days prior to start of study drug (C1D1; cycle is 21 days)
  • Received live vaccine within 4 weeks of C1D1; cycle is 21 days
  • Congenital long measure between Q wave and T wave in the electrocardiogram (QT) syndrome or a corrected Fridericia correction of the QT measure (QTcF) interval of >480 ms at Screening (unless secondary to pacemaker or bundle branch block)
  • 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
  • Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participant inappropriate for study participation or put the participant at risk.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: A Phase 1b, Open-Label, Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of Loncastuximab Tesirine in Combination With R-CHOP in Patients With Previously Untreated Diffuse Large B-cell Lymphoma (LOTIS-8)

The primary objective of this study is to characterize the safety and tolerability of loncastuximab tesirine in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, and identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) for the combination therapy.

Read the detailed description

This is a Phase 1b, open-label, multi-center study in participants with previously untreated DLBCL, with a dose escalation part followed by dose expansion part.

Participants will be treated by loncastuximab tesirine in combination with R CHOP.

The duration of the study participation for each participant is defined as the time from the date of signed written informed consent to the completion of the follow-up period, withdrawal of consent, lost to follow-up, or death, whichever occurs first.

The study will include a Screening Period (of up to 28 days), a Treatment Period of 6 cycles (cycles of 3 weeks), and a Follow-up Period (approximately every 12 week visits) for up to approximately 3 years from end-of-treatment (EOT).

Being tested
Loncastuximab tesirine, Prednisone, Rituximab, Cyclophosphamide, Doxorubicin
Keywords
Diffuse Large B-Cell Lymphoma, Untreated Diffuse Large B-Cell Lymphoma, DLBCL, Loncastuximab Tesirine
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Loncastuximab tesirineDrug

    Also called ADCT-402, ZYNLONTA

    Intravenous (IV) infusion

  • PrednisoneDrug

    Orally via tablet or capsule

  • RituximabDrug

    Intravenous (IV) infusion

  • CyclophosphamideDrug

    Intravenous (IV) infusion

  • DoxorubicinDrug

    Intravenous (IV) infusion

  • VincristineDrug

    Intravenous (IV) infusion

Study groups in NCT04974996
Study groupRoleWhat they receive
Part 1: Dose EscalationExperimentalParticipants will receive escalating doses of loncastuximab tesirine (initial dose of 60 μg/kg and highest dose possibly tested of 150 µg/kg) in combination with R-CHOP (rituximab 375 mg/m^2, cyclophosphamide 750 mg/m^2, doxorubicin 50 mg/m^2, vincristine 1.4 mg/m^2, and prednisone 100 mg/day) according to a standard 3+3 dose escalation design. The dose escalation part will be completed once the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) has been identified.
Receives: Drug: Loncastuximab tesirine; Drug: Prednisone; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine
Part 2: Dose ExpansionExperimentalParticipants will receive the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of loncastuximab tesirine in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as determined in Part 1.
Receives: Drug: Loncastuximab tesirine; Drug: Prednisone; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experience Dose Limiting Toxicities (DLTs) in Part 1

    Measured: Day 1 to Day 21 of Cycle 1, where a cycle is 21 days

  2. Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)

    Frequency and severity of TEAEs and treatment-emergent serious adverse events (SAEs), graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

    Measured: Day 1 up to End of Treatment (up to 30 days after last dose of study treatment in this study or start of a new anticancer therapy, whichever is earlier; approximately 20 weeks)

  3. Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Delay

    Measured: Day 1 up to approximately 18 weeks

  4. Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Interruption

    Measured: Day 1 up to approximately 18 weeks

  5. Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Reduction

    Measured: Day 1 up to approximately 18 weeks

  6. Number of Participants Who Experience a Clinically Significant Change from Baseline in Safety Laboratory Values

    Measured: Baseline (Day 1) to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  7. Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Signs

    Measured: Baseline (Day 1) to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  8. Number of Participants Who Experience a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status

    ECOG performance status will be measured on a scale from grades 0-5, where a higher grade indicates a worse outcome.

    Measured: Baseline (Day 1) to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  9. Number of Participants Who Experience a Clinically Significant Change from Baseline in 12-Lead Electrocardiograms (ECGs)

    Measured: Baseline (Day 1) to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  10. Number of Participants Who Experience a Clinically Significant Change from Baseline in Left Ventricular Ejection Fraction (LVEF) Assessments

    Measured: Baseline (Screening) to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

Secondary outcomes (16)

  1. Overall Response Rate (ORR)

    Measured: Up to approximately 3.5 years

  2. Duration of Response (DOR)

    Measured: Up to approximately 3.5 years

  3. Progression Free Survival (PFS)

    Measured: Up to approximately 3.5 years

  4. Overall Survival (OS)

    Measured: Up to approximately 3.5 years

  5. Complete Response Rate

    Measured: Up to approximately 3.5 years

  6. Average Concentration of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  7. Maximum Concentration (Cmax) of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  8. Time to Maximum Concentration (Tmax) of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  9. Area Under the Concentration-Time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  10. Area Under the Concentration-Time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  11. Area Under the Concentration-Time Curve from Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  12. Apparent Terminal Elimination Half-Life (Thalf) of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  13. Clearance of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  14. Steady-State Volume of Distribution (Vss) of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  15. Accumulation Index of Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

  16. Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine

    Measured: Day 2 to End of Treatment (up to 30 days after last dose of study treatment; approximately 20 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jul 2021
  2. Study start1 Feb 2022 (estimated)
  3. Primary completion11 Mar 2024 (estimated)
  4. Study completion5 May 2027 (estimated)

Why it stopped: Decision to not proceed with study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04974996
Sponsor's protocol ID
ADCT-402-106
Acronym
LOTIS-8
Status last verified
Mar 2022
First submitted
22 Jul 2021
Last updated
29 Mar 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Loncastuximab tesirine, Prednisone and Rituximab in people with Diffuse Large B-Cell Lymphoma, run by ADC Therapeutics S.A. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 29 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experience Dose Limiting Toxicities (DLTs) in Part 1 (time frame: Day 1 to Day 21 of Cycle 1, where a cycle is 21 days). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04974996.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in