Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Behaviors and Mental Disorders

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Aggression

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Obinutuzumab

Immunoglobulins

Pixantrone

Antineoplastic Agents, Immunological

Enzyme Inhibitors

Obinutuzumab: 1000 mg flat dose on day 1, 8, 15 of cycle one and day 1 of subsequent cycles Pixantrone: 50 mg/m² Pixantrone on day 1,8,15 of each 28 d cycle

Obinutuzumab: 1000 mg flat dose on day 1, 8, 15 of cycle one and day 1 of subsequent cycles, Pixantrone: 50 mg/m² Pixantrone on day 1,8,15 of each 28 d cycle

Obinutuzumab and Pixantrone

Georg Hess, MD

The purpose of this study is to evaluate the overall response rate of Obinutuzumab (GA101) in combination with Pixantrone in patients with relapsed aggressive B-cell lymphoma. 70 patients with diffuse large B-cell lymphoma, follicular lymphoma grade IIIB or transformed indolent lymphoma will receive up to 6 cycles of the described combination regimen. Follow up visits are scheduled for up to 3 years.

In patients with multiple relapsed aggressive lymphoma or refractory lymphoma life expectancy is short. Without potent treatment options the remaining life span can be measured in weeks to a few months.

Recently, an increasing number of reports have shown that either single agent use or the incorporation of potentially more potent agents or new approaches aiming at the inhibition of lymphoma specific pathways may help to overcome the current stagnation in the improvement of first and second line therapies. Surprisingly, little efforts have been undertaken to identify optimal standard dose backbone regimens based on currently available and novel drugs, which ideally would combine activity with reasonable safety and tolerability which allows the addition of targeted drugs in the future. Therefore this trial aims to test prospectively one potential combination to evaluate its potency in patients not suitable for intensive treatment.

Obinutuzumab is an anti-CD20 monoclonal antibody which has shown clinical efficacy even in patients failing Rituximab pre-treatment and therefore is an attractive combination partner within chemo-immunotherapy regimen. Pixantrone belongs to the most potent class of cytostatic drugs for the treatment of lymphoma. Given the proven efficacy of both drugs in relapsed aggressive lymphoma as well as the side effect profiles of both drugs, combination treatment seems sufficiently safe and promises significant efficacy.

This is a multicenter, prospective, open-label, non-randomized trial to evaluate the overall response rate of Obinutuzumab (GA101) in combination with Pixantrone in patients with relapsed aggressive B-cell lymphoma. The trial consists of a 28-days screening period, a treatment-period of up to 6 cycles of the combination regiment, including an interim staging prior to cycle 4 and an end of treatment visit 4-6 weeks after the last study-medication application. The response to treatment is measured by results of computer tomography (CT) after cycle 6 or at the individual end of treatment. Structured follow up visits are scheduled for 2 years, afterwards patients will be followed for survival and progression via a simplified survey until the end of the trial.

GOAL: GA101 Plus Pixantrone for Relapsed Aggressive Lymphoma

The GOAL Trial: Rescue Treatment With the Monoclonal Anti CD20-antibody Obinutuzumab (GA101) in Combination With Pixantrone for the Treatment of Patients With Relapsed Aggressive B-cell Lymphoma

The response to treatment is measured by results of computer tomography (CT) for measurable lesions and evaluation for non-measurable lesions after cycle 6 or at the individual end of treatment.

Percentage of patients completing the entire trial treatment

best response either during or post the entire treatment

Progression-free survival rate: The time from first intake/dose of trial medication to first documentation of objective tumor progression or to death due to any cause, whichever occurs first.

* 2-year survival: rate of patients surviving for at least two years after first intake/dose of trial medication.
* Median overall survival: the time between first applications of trial medication to date of death of half of the patients due to any cause

Overall response rate (ORR) in separate germinal-center B-cell-like (GCB)- vs. non GCB-analysis (gene expression profiling (GEP))

Roche Pharma AG

Servier

Johannes Gutenberg University Mainz

Principle Ivestigator

MDV9300 will be administered at a dose of 200 mg by intravenous (IV) infusion every 2 weeks until treatment discontinuation criteria are met.

MDV9300

The purpose of this study is to evaluate the efficacy and safety of MDV9300 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) that have achieved either stable disease or a partial remission following definitive salvage therapy.

Two cohorts of patients will be enrolled: a cohort treated with salvage chemotherapy but considered ineligible for autologous stem cell transplant (ASCT), and a cohort of patients who have received ASCT following salvage chemotherapy.

Efficacy and Safety Study of MDV9300 in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

An International, Phase 2, Open-Label, Efficacy and Safety Study of MDV9300 in Patients With an Incomplete Response Following Salvage Therapy or Autologous Stem Cell Transplantation for Relapsed or Refractory CD20+ Diffuse Large B-Cell Lymphoma

Defined as the proportion of patients in the intent-to-treat population with a complete response (CR) or partial response (PR) attributable to study treatment, as assessed by the independent review committee (IRC).

Defined as the time from the first objective evidence of CR or PR as assessed by the IRC to the first objective evidence of disease progression or death due to any cause, whichever occurs first.

Defined as the time from the date of first study drug infusion to the first objective evidence of disease progression or death due to any cause, whichever occurs first.

Defined as the time from the date of first study drug infusion to the first objective evidence of CR or PR as assessed by the IRC.

Defined as the time from the date of first study drug infusion to death due to any cause.

Safety will be evaluated by incidence and severity of adverse events, including serious adverse events and incidence of permanent treatment discontinuation due to adverse events.

Medivation, Inc.

Lenalidomide

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Drug: Plamotamab will be administered at a lower dose in addition to tafasitamab (12 milligrams \[mg\]/kilograms \[kg\] intravenously) plus lenalidomide (25 mg orally). This cohort was planned to enroll sequentially prior to Part 1B.

Drug: Plamotamab will be administered at the target dose in addition to tafasitamab (12 mg/kg intravenously) plus lenalidomide (25 mg orally). This cohort was planned to enroll sequentially after Part 1A.

Drug: Plamotamab will be administered at protocol defined dose in addition to tafasitamab (12 mg/kg intravenously) plus lenalidomide 25 mg (orally).

Drug: Tafasitamab (12 mg/kg intravenously) plus lenalidomide 25 mg (orally).

Plamotamab

Tafasitamab

Michael Chiarella

The purpose of this study is to investigate the safety and effectiveness of plamotamab when it is given with tafasitamab and lenalidomide in participants with relapsed or refractory DLBCL.

This is a randomized, multicenter, open-label, Phase 2 study of plamotamab combined with tafasitamab plus lenalidomide versus tafasitamab plus lenalidomide in adult participants with DLBCL who have relapsed after or are refractory to at least 1 prior line of therapy, which must have included multi-agent chemoimmunotherapy inclusive of an anti-cluster of differentiation (CD) 20 monoclonal antibody, and who are not candidates for autologous stem-cell transplantation (ASCT), refuse ASCT, or relapse after ASCT.

The study was planned to be performed sequentially, with Part 1A (Safety run-in, with a lower plamotamab dose), Part 1B (Safety run-in, with the target plamotamab dose) and Part 2 (Open-Label, randomized). The study was terminated by the Sponsor during Part 1A of the study. No participants were enrolled in Part 1B or Part 2.

Part 1 Single Arm Multiple Dose Followed by Part 2 Randomized

Phase 2 Study of Plamotamab Combined With Tafasitamab Plus Lenalidomide Versus Tafasitamab Plus Lenalidomide in Relapsed or Refractory (R/R) Diffuse Large-cell B-cell Lymphoma (DLBCL)

A Phase 2 Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of XmAb13676 (Plamotamab) Combined With Tafasitamab Plus Lenalidomide Versus Tafasitamab Plus Lenalidomide in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

An adverse event (AE) was any untoward medical occurrence in a study participant. The AE did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug. AEs may have included the onset of new illness and the exacerbation of preexisting conditions. TEAEs were defined as events with onset dates on or after the start of study treatment or events that were present before the first infusion of study treatment and subsequently worsened in severity. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Cytokine release syndrome was defined as "a supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells". A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Xencor, Inc.

Enrolled Analysis Set: All participants who signed the informed consent form, were determined to be eligible, and received Day -8 tafasitamab dose (Study Day 1). The study was terminated by the Sponsor during Part 1A of the study. No participants were enrolled in Part 1B or Part 2.

Plamotamab was administered at a lower dose in addition to tafasitamab (12 mg/kg intravenously) plus lenalidomide (25 mg orally).

Part 1A: Plamotamab (Lower Dose), Tafasitamab, and Lenalidomide

>=18 years

Age, Customized

Due to the small sample size, data was not reported for participant confidentiality reasons.

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Due to the early termination of the study in Part 1A, only 3 participants enrolled. No participants were enrolled in Part 1B or Part 2. Safety data is limited due to the small sample size. No efficacy data was collected for the secondary outcome measures.

Part 1 A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Part 1 A: Number of Participants With Cytokine Release Syndrome

Plamotamab was administered at a lower dose in addition to tafasitamab (12 milligrams \[mg\]/kilograms \[kg\] intravenously) plus lenalidomide (25 mg orally).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
GOAL: GA101 Plus Pixantrone for Relapsed Aggressive Lymphoma	NCT02499003	Lymphoma, Non-H...	Obinutuzumab an...	18 Years -	Johannes Gutenberg University Mainz
Efficacy and Safety Study of MDV9300 in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)	NCT02653989	Lymphoma, Large... Primary Mediast... Transformed Ind...	MDV9300	18 Years -	Medivation, Inc.
Phase 2 Study of Plamotamab Combined With Tafasitamab Plus Lenalidomide Versus Tafasitamab Plus Lenalidomide in Relapsed or Refractory (R/R) Diffuse Large-cell B-cell Lymphoma (DLBCL)	NCT05328102	Diffuse Large-c...	Plamotamab Tafasitamab Lenalidomide	18 Years -	Xencor, Inc.
Efficacy and Safety Study of MDV9300 in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)	NCT02653989	Lymphoma, Large... Primary Mediast... Transformed Ind...	MDV9300	18 Years -	Medivation, Inc.
GOAL: GA101 Plus Pixantrone for Relapsed Aggressive Lymphoma	NCT02499003	Lymphoma, Non-H...	Obinutuzumab an...	18 Years -	Johannes Gutenberg University Mainz

Spots Global Cancer Trial Database for transformed indolent lymphoma