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B-cell LymphomaPhase 1LONCANCT05270057

Loncastuximab Tesirine in Combination With DA-EPOCH-R in Patients With Previously Untreated Aggressive B-cell Lymphoid Malignancies

A Phase 1 study testing Etoposide, Doxorubicin and Cyclophosphamide in people with B-cell Lymphoma and Burkitt Lymphoma, run by Medical College of Wisconsin at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The overarching hypothesis for this study is that a safe and tolerable dose (i.e., the maximum tolerated dose) will be identified for loncastuximab tesirine in combination with dose-adjusted etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, doxorubicin hydrochloride… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-cell Lymphoma, Burkitt Lymphoma
What is being tested?
Etoposide, Doxorubicin and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
3 sitesUnited States
Study dates
26 Jan 2023to 11 Oct 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Age ≥ 18 years.
  • Adult patients with B-cell lymphoma, specifically one of the following: high-grade B-cell lymphoma with MYC and B-cell lymphoma 2 (BCL2) and/or B cell lymphoma 6 (BCL6) rearrangements; high-grade B-cell lymphoma, not otherwise specified, primary mediastinal diffuse large B-cell lymphoma; Burkitt lymphoma; diffuse large B-cell lymphoma with MYC rearrangement; or Cluster of Differentiation 19 (CD19) -positive plasmablastic lymphoma.
  • Patients must not have received prior multiagent chemotherapy for their lymphoma. Limited palliative radiation is allowed. Corticosteroid therapy in symptomatic patients will be permitted and does not require a washout period. Prephase treatment with cyclophosphamide and corticosteroids or vincristine and corticosteroids is allowed in symptomatic patients.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status criteria of 0-3.
  • Adequate hematological function, defined as absolute neutrophil count (ANC) ≥1 × 103/μL and platelet count ≥50 x 10^3/μL.
  • These requirements do not apply to patients with bone marrow involvement of lymphoma.
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  • Adequate hepatic function: aspartate aminotransferase (AST) / alanine aminotransferase (ALT) / gamma-glutamyl transferase (GGT) ≤ 3 x institutional upper limit of normal (ULN) and bilirubin < 1.5 x ULN, unless due to hepatic involvement with lymphoma or Gilbert's syndrome.
  • Exceptions can be granted from principal investigator for primarily indirect bilirubinemia if due to recent transfusion and/or hemolysis.
  • Creatinine clearance ≥ 30 ml/min calculated using the Cockroft-Gault formula.
  • Left ventricular ejection fraction (LVEF) of ≥50%, assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan.
  • Patients with marrow-only disease will be eligible.
  • Patients rendered no evidence of disease via surgery will be eligible.
  • Central nervous system (CNS) involvement is not considered contraindication for patients with Burkitt lymphoma.
  • Known HIV-positive patients compliant with antiretroviral therapy and with undetectable viral loads will be permitted.
  • Pregnancy It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below.
  • Female patients of childbearing potential must use a highly effective method of contraception during the entire study treatment period and through nine months after the last dose of loncastuximab tesirine.
  • Male patients, even if surgically sterilized (i.e., status postvasectomy), with female partners who are of childbearing potential should use a condom when sexually active during the entire study treatment period and through six months after the last dose of loncastuximab tesirine.
  • Ability to understand a written informed consent document, and the willingness to sign it.

Who cannot join

  • Presence of clinically significant pericardial or pleural effusions, or third space fluid accumulations (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath).
  • Known history of hypersensitivity to CD19 antibody, components of study medication, or DA-EPOCH-R.
  • Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy. These subjects MUST HAVE undetectable HBV viral load to be considered for this protocol.
  • Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load.
  • Breastfeeding or pregnant.
  • Active systemic bacterial, viral, fungal, or other infection requiring systemic treatment at time of screening.
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  • Congenital long QT syndrome or a corrected QT measure (QTc) interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block).
  • Patients diagnosed with another malignancy within three years or with any evidence of residual prior malignant disease (except nonmelanoma skin cancer, non-metastatic prostate cancer, in situ cervical cancer, or ductal or lobular carcinoma in situ). Patients meeting this exclusion criteria may be enrolled after approval from study PI.
  • Significant medical comorbidities such as New York Heart Association class ≥III heart failure, unstable angina, uncontrolled arrhythmias, or severe chronic pulmonary disease.
  • Lymphoma with active CNS involvement at time of screening unless the patient has Burkitt lymphoma.
  • Patient with known intraparenchymal CNS involvement (including those with Burkitt lymphoma).
  • Patients with known Child Pugh Class C hepatic impairment.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Texas Southwestern

    Dallas, Texas, 75390

  • University of Wisconsin School of Medicine and Public Health

    Madison, Wisconsin, 53705

  • Froedtert Hospital & the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: A Multicenter Phase 1, Open-Label Trial of Loncastuximab Tesirine in Combination With DA-EPOCH-R in Patients With Previously Untreated Aggressive B-cell Lymphoid Malignancies

The overarching hypothesis for this study is that a safe and tolerable dose (i.e., the maximum tolerated dose) will be identified for loncastuximab tesirine in combination with dose-adjusted etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), and rituximab (DA-EPOCH-R) for patients with previously untreated aggressive B-cell lymphoid malignancies.

Read the detailed description

This is a multicenter phase 1, open-label trial that will evaluate the safety and tolerability of loncastuximab tesirine in combination with DA-EPOCH-R.

Phase 1a will involve a standard 3+3 dose escalation design to find the maximum tolerated dose (MTD) and/or recommended dose for expansion. The MTD will be determined based on the results of the safety evaluation. No intra-patient dose escalation is allowed.

Phase 1b will involve a cohort expansion at the dose level determined to be the recommended phase 2 dose.

Medical subject headings
Lymphoma, B-Cell, Burkitt Lymphoma

What participants receive

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

  • EtoposideDrug

    Also called Etopophos, Toposar, Vepesid

    Dose level -2=50 mg/m^2; dose level -1=50 mg/m^2; dose level 1=50 mg/m^2; dose level 2=60 mg/m^2; dose level 3=72 mg/m^2; dose level 4=86.4 mg/m^2; dose level 5=103.7 mg/m^2; dose level 6=124.4 mg/m^2; dose level 7=149.3 mg/m^2

  • DoxorubicinDrug

    Also called Lipodox, Lipodox 50, Doxil, Adriamycin

    Dose level -2=10 mg/m^2; dose level -1; dose level -1=10 mg/m^2; dose level 1=10 mg/m^2; dose level 2=12 mg/m^2; dose level 3=14.4 mg/m^17.3 mg/m^2; dose level 4=17.3 mg/m^2; dose level 5=20.7 mg/m^2; dose level 6=24.8 mg/m^2; dose level 7=29.8 mg/m^2.

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar, Endoxan, Procytox

    Dose level -2=480 mg/m^2; dose -1=600 mg/m^2; dose level 1=750 mg/m^2; level 2=900 mg/m^2; level 3=1080 mg/m^2; level 4=1296 mg/m^2; level 5=1555 mg/m^2; level 6=1866 mg/m^2; level 7=2239 mg/m^2.

  • RituximabDrug

    Also called Rituxan, MabThera

    Level -2 through level 7: 375 mg/m^2

  • VincristineDrug

    Also called Oncovin, Vincasar, Marqibo, Leurocristine

    Level -2 through level 7: 0.4 mg/m^2/day

  • PrednisoneDrug

    Also called Deltasone, Orasone, Meticorten, Liquid Pred

    Level -2 through level 7: 60 mg/m^2/twice daily (BID)

  • Loncastuximab Tesirine 0.075 mg/kg by IVDrug

    Also called Zynlonta, ADCT-402, loncastuximab tesirine-lpyl

    Cohort 1: 0.075 mg/kg by IV. The dose-expansion phase will use the maximum-tolerated dose.

  • Loncastuximab tesirine 0.12 mg/kg by IVDrug

    Also called Zynlonta, ADCT-402, loncastuximab tesirine-lpyl

    Cohort 2: 0.12 mg/kg by IV. The dose-expansion phase will use the maximum-tolerated dose.

  • Loncastuximab tesirine 0.15 mg/kg by IVDrug

    Also called Zynlonta, ADCT-402, loncastuximab tesirine-lpyl

    Cohort 3: 0.15 mg/kg by IV The dose-expansion phase will use the maximum-tolerated dose.

Study groups in NCT05270057
Study groupRoleWhat they receive
Loncastuximab Tesirine Dose Escalation 0.075 mg/kg by IV.ExperimentalThe study uses a classic 3+3 dose-escalation design. Three patients will be enrolled into a cohort receiving 0.075 mg/kg by IV. If there is no dose-limiting toxicity (DLT) seen in any of these participants, the trial will enroll additional participants into the next higher dose cohort, which is 0.12 mg/kg by IV. If one patient experiences a DLT at a specific dose, an additional three individuals will be accrued into that same dose cohort. The third dose level is 0.15 mg/kg by IV. DLTs in two or more at a specific dose level indicates that the MTD has been exceeded; dose escalation will not be pursued, and the prior dose level will be expanded to six patients; if there is no more than one patient who experiences a DLT among those six patients, that dose level is considered the MTD.
Receives: Drug: Etoposide; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Vincristine; Drug: Prednisone; Drug: Loncastuximab Tesirine 0.075 mg/kg by IV
Loncastuximab Tesirine Dose Escalation 0.12 mg/kg by IV.ExperimentalThe study uses a classic 3+3 dose-escalation design. Three patients will be enrolled into a cohort receiving 0.075 mg/kg by IV. If there is no dose-limiting toxicity (DLT) seen in any of these participants, the trial will enroll additional participants into the next higher dose cohort, which is 0.12 mg/kg by IV. If one patient experiences a DLT at a specific dose, an additional three individuals will be accrued into that same dose cohort. The third dose level is 0.15 mg/kg by IV. DLTs in two or more at a specific dose level indicates that the MTD has been exceeded; dose escalation will not be pursued, and the prior dose level will be expanded to six patients; if there is no more than one patient who experiences a DLT among those six patients, that dose level is considered the MTD.
Receives: Drug: Etoposide; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Vincristine; Drug: Prednisone; Drug: Loncastuximab tesirine 0.12 mg/kg by IV
Loncastuximab Tesirine Dose Escalation 0.15 mg/kg by IV.ExperimentalThe study uses a classic 3+3 dose-escalation design. Three patients will be enrolled into a cohort receiving 0.075 mg/kg by IV. If there is no dose-limiting toxicity (DLT) seen in any of these participants, the trial will enroll additional participants into the next higher dose cohort, which is 0.12 mg/kg by IV. If one patient experiences a DLT at a specific dose, an additional three individuals will be accrued into that same dose cohort. The third dose level is 0.15 mg/kg by IV. DLTs in two or more at a specific dose level indicates that the MTD has been exceeded; dose escalation will not be pursued, and the prior dose level will be expanded to six patients; if there is no more than one patient who experiences a DLT among those six patients, that dose level is considered the MTD.
Receives: Drug: Etoposide; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Vincristine; Drug: Prednisone; Drug: Loncastuximab tesirine 0.15 mg/kg by IV
Loncastuximab Tesirine Dose Escalation Maximum Tolerated DoseExperimentalThe study uses a classic 3+3 dose-escalation design. Three patients will be enrolled into a cohort receiving 0.075 mg/kg by IV. If there is no dose-limiting toxicity (DLT) seen in any of these participants, the trial will enroll additional participants into the next higher dose cohort, which is 0.12 mg/kg by IV. If one patient experiences a DLT at a specific dose, an additional three individuals will be accrued into that same dose cohort. The third dose level is 0.15 mg/kg by IV. DLTs in two or more at a specific dose level indicates that the MTD has been exceeded; dose escalation will not be pursued, and the prior dose level will be expanded to six patients; if there is no more than one patient who experiences a DLT among those six patients, that dose level is considered the MTD. This dose will be added to this record when it is determined.
Receives: Drug: Etoposide; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Vincristine; Drug: Prednisone; Drug: Loncastuximab Tesirine 0.075 mg/kg by IV; Drug: Loncastuximab tesirine 0.12 mg/kg by IV; Drug: Loncastuximab tesirine 0.15 mg/kg by IV
Dose Expansion PhaseExperimentalSubjects will receive the recommended phase 2 dose (RP2D) identified from dose-escalation phase. This dose will be added to this record when it is determined.
Receives: Drug: Etoposide; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Vincristine; Drug: Prednisone; Drug: Loncastuximab Tesirine 0.075 mg/kg by IV; Drug: Loncastuximab tesirine 0.12 mg/kg by IV; Drug: Loncastuximab tesirine 0.15 mg/kg by IV

What is being measured

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

  1. The maximum tolerated dose (MTD).

    MTD is defined as the highest dose level where zero of the first three patients treated or ≤1 of the first six patients treated had a dose-limiting toxicity (DLT) during cycle 1 of phase 1a.

    Measured: Up to 21 days (one cycle) for each dosing cohort.

  2. The number of dose-limiting toxicities (dose-escalation phase only).

    A dose-limiting toxicity is defined as any of the following within 21 days after administration of the first dose of loncastuximab tesirine in phase 1a part 1a only (except any toxicity clearly due to disease or other causes): adverse events and lab data, using Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.

    Measured: Up to 21 days (one cycle).

Timeline

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

  1. First posted8 Mar 2022
  2. Study start26 Jan 2023
  3. Primary completion28 May 2025
  4. Study completion11 Oct 2027 (estimated)

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
Model description
Phase 1a will involve a standard 3+3 dose escalation design to find the maximal tolerated dose (MTD) and/or recommended dose for expansion.
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05270057
Sponsor's protocol ID
PRO43132
Acronym
LONCA
Status last verified
Oct 2026
First submitted
24 Feb 2022
Last updated
14 Oct 2026
Results posted
No
Data monitoring committee
Yes
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 Etoposide, Doxorubicin and Cyclophosphamide in people with B-cell Lymphoma and Burkitt Lymphoma, run by Medical College of Wisconsin at 3 sites 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 18 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

This study is still under way. Results are not available in the source record yet.

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?

The maximum tolerated dose (MTD). (time frame: Up to 21 days (one cycle) for each dosing cohort.). The study lists 2 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 NCT05270057.

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 14 Oct 2026.

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