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: