Loncastuximab Tesirine in Combination with Rituximab for the Treatment of Relapsed/Refractory Follicular Lymphoma
This phase II trial tests whether loncastuximab tesirine in combination with rituximab works to shrink tumors in patients with follicular lymphoma at the time of relapse or progression. Loncastuximab is a novel antibody-drug conjugate composed of a humanized anti-CD19 conjugated to a cytotoxic dimer. After binding to the tumor cells, the antibody is internalized, the cytotoxic drug is released, and the cancer cells are killed. CD19 is ubiquitously expressed in follicular lymphoma, making it an excellent target. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving loncastuximab tesirine and rituximab may work better in treating patients with follicular lymphoma.
Inclusion Criteria
- Men and women >= 18 years of age
- Patients must have histologic confirmation of FL (grade 1, 2 and 3A) defined by the World Health Organization (WHO) classification. 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 (r/r) FL previously treated with >= 1 line of systemic therapy having >= 1 Groupe d’Etude des Lymphomes Folliculaires (GELF) criteria for therapy and/or relapsed/progression of disease within 24 months of frontline therapy (POD24)
- Baseline FDG-PET/CT scans must demonstrate positive lesions compatible with computed tomography (CT) defined anatomical tumor sites. Patients should have at least one measurable site of disease per Lugano classification. (Note: The measurable site of disease could be determined by the treating physician/study investigator.)
- Patient should have >= 1 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/mm^3) * Leukemia (> 5000 lymphoma cells/mm^3) * Bone lesions detected on FDG-PET/CT will be also consider an indication for treatment
- Progression or relapse within 24 months (POD24) of frontline treatment in patients previously treated with >= 1 line of systemic therapy
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of greater than 6 weeks
- Absolute neutrophil count >= 1000/mm^3 (unless due to lymphoma involvement of the bone marrow or spleen)
- Platelets >= 100,000 platelets/mm^3 or >= 50,000 platelets/mm^3 in case of bone marrow or spleen involvement by lymphoma
- Hemoglobin >= 10 g/dL or >= 8 g/dL in case of bone marrow or spleen involvement by lymphoma
- Total bilirubin < 1.5 x within normal institutional limits (unless due to lymphoma involvement of liver or a known history of Gilbert’s disease)
- Gamma-glutamyl transpeptidase (GGT)/aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN) or =< 5 x institutional ULN in the presence of liver involvement by lymphoma
- Creatinine within normal institutional limits or creatinine clearance >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (unless due to lymphoma)
Exclusion Criteria
- FL grade 3B or transformed FL
- > 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 hepatitis 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
Additional locations may be listed on ClinicalTrials.gov for NCT04998669.
Locations matching your search criteria
United States
Florida
Coral Gables
Coral Springs
Deerfield Beach
Hollywood
Miami
Plantation
PRIMARY OBJECTIVE:
I. To determine the complete response (CR) rate at end of induction phase (around week 12 of treatment) in patients with relapsed or refractory (r/r) follicular lymphoma (FL) previously treated with >= 1 line of systemic therapy receiving the combined treatment loncastuximab tesirine plus rituximab by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT).
SECONDARY OBJECTIVES:
I. To determine the overall response rate (ORR; CR + partial response [PR]) at end of induction phase in FL.
II. To confirm the safety and tolerability of combined treatment loncastuximab tesirine plus rituximab in patients with r/r FL.
III. To estimate the progression-free survival (PFS) and overall survival (OS) rate at 2 years.
EXPLORATORY OBJECTIVES:
I. Correlate efficacy endpoints such as CR, ORR, PFS and OS with the following:
Ia. Metabolic tumor volume (MTV) by FDG-PET/CT;
Ib. Circulating tumor deoxyribonucleic acid (ctDNA);
Ic. Results of genetic interrogation in relapsed biopsy if available;
Id. Health-related quality of life (HRQoL) assessment during study period.
OUTLINE:
INDUCTION PHASE: Patients receive loncastuximab tesirine intravenously (IV) on day 1 of cycles 1-4, and rituximab IV or rituximab and hyaluronidase human subcutaneously (SC) on days 1, 8, and 15 of cycle 1 and day 1 of cycle 2. Treatment repeats every 21 day for up to 4 cycles in the absence of disease progression of unacceptable toxicity.
MAINTENANCE PHASE: Patients undergo maintenance phase treatment in one of two ways (protocol version 3 treatment or protocol version 5 treatment), depending on time of enrollment to study.
PROTOCOL VERSION 3 MAINTENANCE TREATMENT:
MAINTENANCE PHASE 1 (CYCLE 5): Patients with complete response (CR) or partial response (PR) receive loncastuximab tesirine IV on day 1 of weeks 1, 4, and 7 and rituximab IV or rituximab and hyaluronidase human SC on day 1 of week 1 in the absence of disease of progression or unacceptable toxicity.
MAINTENANCE PHASE 2 (CYCLES 6 & 7): Patients with CR receive rituximab IV or rituximab and hyaluronidase human SC on day 1 of week 1 in each cycle. Patients with PR receive loncastuximab tesirine IV on day 1 of weeks 1, 4, and 7 in each cycle and rituximab IV or rituximab and hyaluronidase human SC on day 1 of week 1 in each cycle. Treatment repeats every 9 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity.
PROTOCOL VERSION 5 MAINTENANCE TREATMENT:
MAINTENANCE PHASE (CYCLES 5 & 6): Patients with CR or PR receive loncastuximab tesirine IV on days 1 and 22 of cycle 5 and rituximab IV or rituximab and hyaluronidase human SC on day 1 of cycles 5 and 6. Treatment repeats every 56 days (8 weeks) for 2 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo FDG-PET/CT and blood sample collection throughout the study and may undergo bone marrow aspiration and biopsy and/or tumor biopsy throughout the study.
After completion of study treatment, patients are followed up every 3 or 6 months for 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationUniversity of Miami Miller School of Medicine-Sylvester Cancer Center
Principal InvestigatorJuan Pablo Alderuccio
- Primary ID20201130
- Secondary IDsNCI-2021-12482
- ClinicalTrials.gov IDNCT04998669