Overview

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

Status:
Not yet recruiting
Trial end date:
2028-05-01
Target enrollment:
0
Participant gender:
All
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 (hydroxydaunorubicin), and rituximab (DA-EPOCH-R) for patients with previously untreated aggressive B-cell lymphoid malignancies.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Medical College of Wisconsin
Treatments:
Cyclophosphamide
Doxorubicin
Etoposide
Liposomal doxorubicin
Loncastuximab tesirine
Prednisone
Rituximab
Vincristine
Criteria
Inclusion Criteria:

1. Age ≥ 18 years.

2. 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.

3. 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.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status criteria of 0-3 (see
Appendix 1).

5. Adequate hematological function, defined as absolute neutrophil count (ANC) ≥1 ×
103/μL and platelet count ≥50 x 103/μL.

- These requirements do not apply to patients with bone marrow involvement of
lymphoma.

6. Adequate hepatic function: aspartate aminotransferase (AST) / alanine aminotransferase
(ALT) / gamma-glutamyl transferase (GGT) ≤ 3 x institutional upper limit of normal
(ULN) and bilirubin < 2 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.

7. estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73sqm.

8. Left ventricular ejection fraction (LVEF) of ≥45%, assessed by echocardiography or
cardiac multi-gated acquisition (MUGA) scan.

9. Patients with marrow-only disease will be eligible.

10. Patients rendered no evidence of disease via surgery will be eligible.

11. Central nervous system (CNS) involvement is not considered contraindication for
patients with Burkitt lymphoma.

12. Known HIV-positive patients compliant with antiretroviral therapy and with
undetectable viral loads will be permitted.

13. 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.

14. Ability to understand a written informed consent document, and the willingness to sign
it.

Exclusion Criteria: