Description:
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.
Title
- Brief Title: Loncastuximab Tesirine in Combination With Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma
- Official Title: Phase 2, Single-arm, Open-label, Study of Loncastuximab Tesirine in Combination With Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
20201130
- NCT ID:
NCT04998669
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Loncastuximab tesirine | ADCT-402 | Loncastuximab tesirine + Rituximab |
Rituximab | Rituxan | Loncastuximab tesirine + Rituximab |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | - Loncastuximab tesirine
- Rituximab
|
Eligibility Criteria
Inclusion Criteria:
1. Men and women ≥ 18 years of age.
2. Patients must have histologic confirmation of Cluster of Differentiation (CD)19 and
CD20-positive Follicular Lymphoma (FL) (grade 1, 2 and 3A)
3. 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,
Progression of Diseases within 24 months (POD24), or second relapse.
4. 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.
5. 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
6. Progression or relapsed within 24 months after FL diagnosis in patients previously
treated with ≥1 line of systemic therapy; or
7. Second FL relapse/progression after ≥1 line of systemic therapy.
8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
9. Life expectancy of greater than 6 weeks.
10. Patients must have normal organ and marrow function as defined below,
- Absolute neutrophil count ≥1000/mm3 (unless due to lymphoma involvement of the
bone marrow or spleen).
- Platelets ≥100,000/mm3.
- Hemoglobin ≥ 10 g/dL or ≥8 g/dL in case of bone marrow 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)/(SGOT)/Alanine Aminotransferase (ALT)(SGPT) ≤ 2.5 × institutional upper
limit of normal.
- Creatinine within normal institutional limits, or creatinine clearance ≥40
mL/min/1.73 m2 for patients with creatinine levels above institutional normal
(unless due to lymphoma).
Exclusion Criteria:
1. FL grade 3B or transformed FL.
2. Patients with standardized uptake value (SUV) ≥ 14 on FDG-PET/CT and inaccessible
biopsy site.
3. > 2 lines of systemic immunochemotherapy for treatment of FL.
4. Patients with clinically significant pleural effusions and/or ascites requiring
drainage or associated with shortness of breath.
5. Patients receiving any other investigational agents.
6. Patients with known central nervous system involvement of lymphoma.
7. 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).
8. Breastfeeding or pregnant women.
9. 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.
10. Human immunodeficiency virus (HIV) infection.
11. Patients with impaired decision-making capacity.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants achieving Complete Response (CR) |
Time Frame: | 12 weeks |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Number of participants achieving CR or PR |
Time Frame: | Week 12 |
Safety Issue: | |
Description: | Overall response rate (ORR) will be reported as the number of participants achieving complete response (CR) or partial response (PR) by the end of the induction phase, week 12. Response to therapy will be assessed using Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) (FDG-PET)/ Computerized Tomography (CT) following Lugano 2014 criteria. |
Measure: | Incidence of Treatment-Related Adverse Events |
Time Frame: | Up to 13 months |
Safety Issue: | |
Description: | Safety of the intervention will be reported as the incidence of treatment-related toxicity, including serious adverse events (SAEs) and adverse events (AEs), in study participants using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion. |
Measure: | Progression-free Survival (PFS) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Progression-Free Survival (PFS) is defined as the elapsed time from the date of starting treatment (Cycle 1 Day 1) until disease progression or death (whichever occur first). |
Measure: | Overall Survival (OS) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Overall survival (OS) will be defined as the elapsed time from the date of starting treatment (Cycle 1 Day 1) until death. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Juan P. Alderuccio, MD |
Last Updated
August 10, 2021