Loncastuximab Tesirine in Combination With Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma

NCT04998669 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20201130
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this research is to see if Loncastuximab Tesirine in combination with Rituximab will result in higher complete response rate when given to treat follicular lymphoma.

Conditions

Follicular Lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of participants achieving Complete Response (CR)

  Complete Response rate will be reported as the number of participants achieving complete response (CR) to study therapy. Response to therapy will be assessed using Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) (FDG-PET)/ Computerized Tomography (CT) following Lugano 2014 criteria by week 12 of treatment.

  12 weeks

Secondary Outcomes (4)

• Number of participants achieving CR or PR

  Week 12

• Incidence of Treatment-Related Adverse Events

  Up to 13 months

• Progression-free Survival (PFS)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

Study Arms (1)

Loncastuximab tesirine + Rituximab

EXPERIMENTAL

During the 12-week Induction Phase (Cycles 1 to 4), participants will receive loncastuximab tesirine on days 1 of each 3-week cycle for Cycles 1 through 4; and rituximab on days 1, 8, 15 of Cycle 1 and day 1 of Cycle 2. Maintenance Phase 1 (Cycle 5) is 8 weeks: Participants achieving complete response (CR) or partial response (PR) during the Induction Phase will receive loncastuximab tesirine once every 3-weeks; and rituximab once during week 7 or 8. Participants achieving a response of Stable Disease (SD) or Progressive Disease (PD) will be taken off treatment. Maintenance Phase 2 (Cycles 6 and 7) is 16 weeks: * Participants achieving CR during Maintenance Phase 1 receive rituximab once during week 7 or 8 of Cycles 6 and 7. * Participants achieving PR during Maintenance Phase 1 receive loncastuximab tesirine once every 3-weeks over each 8 week cycle; and rituximab once during week 7 or 8 of Cycles 6 and 7. * Participants achieving SD or PD will be taken off treatment.

Drug: Loncastuximab tesirine; Drug: Rituximab

Interventions

Loncastuximab tesirine DRUG

Induction Phase (Cycles 1 through 4): * 150 μg/Kg of loncastuximab tesirine administered via intravenous infusion (given as per treatment guidelines) on Days 1 of a 3-week cycle during Cycles 1 and 2. * 75 μg/Kg of loncastuximab tesirine administered via intravenous infusion (given as per treatment guidelines) on Days 1 of a 3-week cycle during Cycles 3 and 4. Maintenance Phase 1 (Cycle 5): For participants achieving CR or PR, 75 μg/Kg of loncastuximab tesirine administered via intravenous infusion (given as per treatment guidelines). on Day 1 on Week 1, 4, 7 of a 8-week cycle. Maintenance Phase 2 (Cycle 6 \& 7): For participants achieving PR, 75 μg/Kg of loncastuximab tesirine administered via intravenous infusion (given as per treatment guidelines) on Day 1 on Week 1, 4, 7 of a 8-week cycle.

Also known as: ADCT-402

Loncastuximab tesirine + Rituximab

Rituximab DRUG

Induction Phase (Cycles 1 through 4): 375 mg/m2 rituximab on days 1, 8, 15 of cycle 1 and day 1 of cycle 2 via intravenous infusion (given as per treatment guidelines) or subcutaneous 1400 mg/23,400 units hyaluronidase during Cycles 1 and 2, per discretion of treating physician. Rituximab will not be administered during Cycles 3 and 4. Maintenance Phase 1 (Cycle 5): Participants achieving a response of PR or CR will receive 375 mg/m2 rituximab during week 1 of a 8-week cycle via intravenous infusion (given as per treatment guidelines) or subcutaneous 1400 mg/23,400 units hyaluronidase, per discretion of treating physician. Maintenance Phase 2 (Cycles 6 and 7): Participants achieving a response of PR or CR will receive 375 mg/m2 rituximab during week 1 of each 8-week cycle via intravenous infusion (given as per treatment guidelines) or subcutaneous 1400 mg/23,400 units hyaluronidase, per discretion of treating physician.

Also known as: Rituxan

Loncastuximab tesirine + Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥ 18 years of age.
• Patients must have histologic confirmation of Follicular Lymphoma (FL) (grade 1, 2 and 3A). Note: Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy.
• Patients with relapsed or refractory FL previously treated with ≥1 line of systemic therapy having ≥ 1 Groupe d'Etude des Lymphomes (GELF) criteria for therapy, or Progression of Diseases within 24 months (POD24), or second relapse.
• Baseline FDG-PET/CT scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites. Patients should have at least one measurable site of disease per Lugano classification.
• Patient should have ≥ 1 Groupe d'Etude des Lymphomes (GELF) criteria for treatment initiation).
• Involvement of ≥3 nodal sites, each with diameter of ≥3 cm
• Any nodal or extranodal tumor mass with a diameter of ≥7 cm
• B symptoms (fever ≥ 38 degrees Celsius of unclear etiology, night sweats, weight loss \> 10% within the prior 6 months).
• Risk of local compressive symptoms that may result in organ compromise
• Splenomegaly or splenic lesion without splenomegaly
• Leukopenia (leukocytes \< 1000/mm3)
• Leukemia (\> 5.000 lymphoma cells/mm3)
• Bone lesions detected on FDG-PET/CT; or
• Progression or relapse within 24 months of frontline treatment in patients previously treated with ≥1 line of systemic therapy; or
• Second FL relapse/progression after ≥1 line of systemic therapy. These patients will be eligible independently of GELF criteria and POD24.

You may not qualify if:

• FL grade 3B or transformed FL.
• \[Removed\]
• ≥ 6 lines of systemic immunochemotherapy for treatment of FL.
• Patients with clinically significant pleural effusions and/or ascites requiring drainage or associated with shortness of breath.
• Patients receiving any other investigational agents.
• Patients with known central nervous system involvement of lymphoma.
• Uncontrolled intercurrent illness such as: history of Myocardial Infarction (MI) in the last 6 months, congestive heart failure New York Heart Association (NYHA) Class III-IV, uncontrolled or symptomatic arrhythmia, stroke in last 6 months, liver cirrhosis, and autoimmune disorder requiring immunosuppression or long-term corticosteroids (\>10 mg daily prednisone equivalent).
• Breastfeeding or pregnant women.
• Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody will need a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.) Hepatitis C antibody positive patients are eligible if PCR is negative. Hepatitis B core antibody (+) patients without evidence of HBsAg or Hep B PCR (+) are eligible with appropriate Hepatitis B reactivation prophylaxis.
• History of Human immunodeficiency virus (HIV) infection. Note: HIV screening test is optional
• Patients with impaired decision-making capacity.

Sponsors & Collaborators

• Juan P. Alderuccio, MD: lead
• ADC Therapeutics S.A.: collaborator

Study Sites (5)

Florida Cancer Specialists and Research Institute

Fort Myers, Florida, 33916, United States

NOT YET RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

RECRUITING

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

NOT YET RECRUITING

Related Publications (1)

• Alderuccio JP, Alencar AJ, Schatz JH, Kuker RA, Pongas G, Reis IM, Lekakis LJ, Spiegel JY, Sandoval-Sus J, Beitinjaneh A, Stanchina MD, Trabolsi A, Lossos IS, Rosenblatt JD, Lessen DS, Moskowitz CH. Loncastuximab tesirine with rituximab in patients with relapsed or refractory follicular lymphoma: a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2025 Jan;12(1):e23-e34. doi: 10.1016/S2352-3026(24)00345-4. Epub 2024 Dec 7.

  PMID: 39662486 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

loncastuximab tesirine; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Juan P Alderuccio, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juan P Alderuccio, MD

CONTACT

305-243-5995; jalderuccio@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 7, 2021
• First Posted: August 10, 2021
• Study Start: February 11, 2022
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2030
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)