CTEP 10590, NORM: Nodular Lymphocyte Predominant Hodgkin Lymphoma Patients Treated in a Randomized Phase II Trial with Either Rituximab or Mosunetuzumab
Bibliographic record
Abstract
Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) expresses CD20 and is characterized by an indolent disease course, similar to indolent B-cell non-Hodgkin lymphoma (iNHL). NLPHL often affects young patients, who have an excellent prognosis irrespective of therapy and are frequently overtreated with cytotoxic therapies. Overall, 77% of causes of death of NLPHL patients treated in the trials HD7-HD15 were due to second malignancies and nonmalignant conditions possibly associated with radiotherapy (RT) and/or chemotherapy used for classical Hodgkin lymphoma (cHL). Mosunetuzumab is an anti-CD20/CD3 T-cell-dependent bispecific antibody with a complete response (CR) rate of 65.7% in relapsed/refractory iNHL (Budde et al. JCO 2024). The discovery of novel efficacious targeted therapies for NLPHL is essential to avoid overtreatment, decrease toxicities, and improve patient quality of life. Objectives: This study aims to compare the progression-free survival (PFS), safety and antitumor activity of mosunetuzumab versus rituximab in NLPHL patients. Methods: We are conducting a phase II, randomized, open label, multicenter trial NCT05886036 evaluating either rituximab or mosunetuzumab for patients 18 years or older with previously untreated NLPHL stage IB to IV or previously treated NLPHL of any stage, requiring systemic therapy. Patients with transformed NLPHL and patients previously treated with rituximab are excluded. Patients will receive either rituximab (375 mg/m2 IV on Cycle 1 Day 1, followed by rituximab 1400 mg/hyaluronidase 23,400 units SC on C1D8-C2D22, 2 cycles of weekly rituximab 4x, 8 weeks apart) or mosunetuzumab (SC with step-up dosing Cycle 1 Day 1, 8, and 15 and Day 1 of subsequent cycles (5/45/45 mg), up to 8 cycles). Consolidative RT based on disease response for patients with limited stage is allowed, if declared prior to randomization (30 Gy for patients with CR, 36-40 Gy for patients with partial response [PR]). PET-CT imaging will be performed to assess response according to the Lugano classification at 12 weeks (interim assessment) and at 25 weeks (end of treatment (EOT) assessment). For patients with disease progression at the time of the interim assessment, crossover to the opposite arm of the trial (start from cycle 1 day 1) is permitted if transformation is excluded and the treating physician estimates that there is potential clinical benefit to continuing therapy on the trial. The primary endpoint is the 2-year PFS. Secondary endpoints include the response rate at the interim and EOT, landmark survival outcomes and safety. Exploratory analyses include assessing molecular response by sequencing cell-free DNA, RNA-sequencing and whole exome sequencing and assessing the association of baseline FDG-PET/CT measurements including metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax), in combination with other risk factors, with PFS and overall survival. We based our sample size justification on a log rank test comparing PFS between the two treatment groups with assumed 2-year PFS rates of 50% (rituximab) versus 75% (mosunetuzunab) with a one-sided type I error rate of 10% and 85% power; accrual period of 3 years and maximum trial duration of 5 years. The expected sample size is 56.1 under the null hypothesis and 61.9 under the alternative hypothesis. Randomization will be 1:1 and the permuted block randomization will be used to balance the stratification factors of: disease stages I/II and III/IV, consolidative RT versus no RT (only for stages I/II patients) and frontline versus relapsed/refractory. The study is open for accrual in the US and Canada since 2024.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".