Phase 2 Study of Glofitamab Monotherapy & With Polatuzumab Vedotin, Pirtobrutinib, or Atezolizumab in Richter's Transformation
Eligible age
18+ yrs
Accepts
All genders
Locations
4 states
Healthy volunteers
No
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About this study
This research is being done to evaluate Glofitamab by itself or in combination with Polatuzumab Vedotin, Pirtobrutinib, or Atezolizumab as possible treatments for Chronic Lymphocytic Leukemia (CLL) that has transformed into Richter's Transformation (RT). The names of the study drugs involved in this research study are: * Glofitamab (a T-cell bispecific humanized monoclonal antibody) * Obinutuzumab (a humanized glycoengineered type II anti-CD20 monoclonal antibody) * Polatuzumab vedotin (an antibody-drug conjugate) * Pirtobrutinib (a selective inhibitor of BTK) * Atezolizumab (a humanized immunoglobulin monoclonal antibody) * Tocilizumab (a recombinant, humanized, anti-human monoclonal antibody)
Sponsor: Christine Ryan
You may qualify if…
- ✓ Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as per IW-CLL 2018 criteria with biopsy proven transformation to large B-cell lymphoma (LBCL), consistent with Richter's Transformation. The diagnostic sample must be reviewed by the treating institution.
- ✓ Tumor sample may be obtained by core needle or excisional surgical biopsy.
- ✓ A fresh biopsy is encouraged, but an archival sample is acceptable if the following provisions are met: 1) availability of a tumor-containing formalin-fixed, paraffin-embedded (FFPE) tissue block, 2) if the tumor containing FFPE tissue block cannot be provided in total, sections from this block should be provided.
- ✓ Biopsy can be obtained up to 3 months prior to first day of treatment.
- ✓ Measurable disease, defined as ≥1 measurable nodal lesion (long axis \>1.5 cm or short axis \>1.0 cm) or ≥1 measurable extra-nodal lesion (long axis \>1.0 cm) on PET, CT, or magnetic resonance imaging (MRI). Disease should be FDG-avid based on PET.
- ✓ Cohort-specific eligibility criteria:
- ✓ Glofitamab monotherapy cohort: Patients with either relapsed/refractory or previously untreated Richter's Transformation.
- ✓ Glofitamab + polatuzumab vedotin cohort: Patients with previously untreated RT. After the first 10 patients are enrolled in this cohort irrespective of prior BTKi exposure status, the remainder of the patients enrolled to this cohort must have previously untreated RT and no prior BTK inhibitor. Patients cannot have prior polatuzumab vedotin exposure.
You may not qualify if…
- ✕ Patients with the Hodgkin variant transformation of CLL will be excluded.
- ✕ No prior anti-CD20 bispecific antibody is allowed. No prior polatuzumab vedotin is allowed for patients in the polatuzumab vedotin-containing combination arm. No prior atezolizumab therapy is allowed for patients in the atezolizumab-containing combination arm. No prior pirtobrutinib is allowed for patients in the pirtobrutinib-containing arm.
- ✕ Subject has received any of the following within 14 days or 5 drug half-lives (whichever is shortest) prior to the first dose of treatment: investigational agents, targeted therapies, e.g. tyrosine kinase inhibitors, systemic immunotherapeutic/immunostimulating agents, including, but not limited to, CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, radio-immunoconjugates, antibody-drug conjugates1, immune/cytokines and monoclonal antibodies. Patients who are currently receiving treatment with an agent targeting Bruton's tyrosine kinase may continue this agent until the day prior to starting treatment, to reduce the risk of tumor flare on treatment cessation (patients in the pirtobrutinib combination arm may not have received an antibody-drug conjugate within 28 days prior to the first dose of study treatment).
- ✕ Prior treatment with CAR T-cell therapy within 30 days before first study treatment administration.
- ✕ Subject has not recovered to less than Grade 1 clinically significant adverse effect(s)/toxicity from prior anti-cancer therapy including immunotherapy, with the exception of alopecia, endocrinopathy managed with replacement therapy, and stable vitiligo.
- ✕ Patients with bulky cervical adenopathy that is compressing the upper airway and could result in significant further airway compression during a tumor flare event.
- ✕ History of other malignancies, except:
- ✕ CLL/SLL
Where it's recruiting
Source: ClinicalTrials.gov · NCT06043674 · last updated 2026-10-21