A Phase 3 Study to Assess Efficacy and Safety of Tafasitamab Plus Lenalidomide and Rituximab Compared to Placebo Plus Lenalidomide and Rituximab in Patients With Relapsed/Refractory (R/R) Follicular Lymphoma or Marginal Zone Lymphoma.

Study Overview
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Brief Summary
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This is a Phase 3 double-blind, placebo-controlled, randomized study designed to investigate whether tafasitamab and lenalidomide as an add-on to rituximab provides improved clinical benefit compared with lenalidomide as an add-on to rituximab in patients with R/R FL Grade 1 to 3a or R/R MZL.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tafasitamab Plus Lenalidomide in Addition to Rituximab Versus Lenalidomide in Addition to Rituximab in Patients With Relapsed/Refractory (R/R) Follicular Lymphoma Grade 1 to 3a or R/R Marginal Zone Lymphoma

Conditions
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Follicular Lymphoma, Marginal Zone Lymphoma

Intervention / Treatment
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* Drug: tafasitamab
* Drug: rituximab
* Drug: lenalidomide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Grade 1, 2, or 3a FL or nodal MZL, splenic MZL, or extra nodal MZL Willingness to avoid pregnancy or fathering children In the opinion of the investigator, be able and willing to receive adequate mandatory prophylaxis and/or therapy for thromboembolic events (eg, aspirin 70-325 mg daily or low-molecular-weight heparin) Previously treated with at least 1 prior systemic anti-CD20 immunotherapy or chemo-immunotherapy Documented relapsed, refractory, or PD after treatment with systemic therapy ECOG performance status of 0 to 2 Exclusion Criteria: Women who are pregnant or breastfeeding. Any histology other than FL and MZL or clinical evidence of transformed lymphoma Prior non-hematologic malignancy Congestive heart failure HCV positivity, chronic HBV infection or history of HIV infection Active systemic infection CNS lymphoma involvement Any systemic anti-lymphoma and/or investigational therapy within 28 days prior to the start of Cycle 1 Prior use of lenalidomide in combination with rituximab

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A : tafasitamab + rituximab + lenalidomide<br>Adult patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Grade 1 to 3a or R/R Marginal Zone Lymphoma (MZL) | Drug: tafasitamab<br>* tafasitamab will be administered IV for 12 cycles<br>* Other names: MOR00208;Drug: rituximab<br>* Rituximab will be administered IV on cycles 1 - 5<br>Drug: lenalidomide<br>* Lenalidomide will be administered PO for 12 cycles<br>|
| Placebo Comparator: Arm B : placebo+rituximab+lenalidomide<br>Adult patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Grade 1 to 3a or R/R Marginal Zone Lymphoma (MZL) | Drug: rituximab<br>* Rituximab will be administered IV on cycles 1 - 5<br>Drug: lenalidomide<br>* Lenalidomide will be administered PO for 12 cycles<br>Drug: placebo<br>* placebo will be administered IV for 12 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) in FL population | Defined as the time from randomization to first documented disease progression, or death from any cause, whichever occurs first. | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) in FL and MZL populations | Defined as the time from randomization to first documented disease progression, or death from any cause, whichever occurs first. | Up to 6 years | 
| Complete Response in FL population | Defined as number of participants with complete response par Positron Emission Tomography(PET) at the end of treatment visit | Up to 6 years | 
| Minimal Residual Disease-negativity rate in FL and MZL Population | Defined as less than 1 residual tumor cell per 10^4 normal cells in peripheral blood and bone marrow. | 14 months | 
| Overall Survival in FL Population | Defined as survival from time of study randomization to death of any cause. | Up to 6 years | 
| Complete Response in Overall population | Defined as number of participants with complete response par Positron Emission Tomography(PET) at the end of treatment visit | Up to 6 years | 
| Overall Survival in overall Population | Defined as survival from time of study initiation to death of any cause. | Up to 6 years | 
| Best Overall Response Rate in FL and overall population | Defined as proportion of participants whose best overall response was a complete response (CR) or partial response (PR). | Up to 6 years | 
| Duration of Response in FL and overall population | Defined as the time to the first response to evidence of progression. | Up to 6 years | 
| Quality-of-Life Assessments in FL and overall populations | Defined as a patient self evaluation questionnaire | Up to 6 years | 
| Safety: Number of participants with TEAE's | Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment up to 30 days after last dose of study treatment. | 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MOR00208, INCMOR00208, tafasitamab