Clinical trial for Chronic Lymphocytic Leukemia
Official title Phase 2 Study of Glofitamab Monotherapy & With Polatuzumab Vedotin, Pirtobrutinib, or Atezolizumab in Richter's Transformation
ClinicalTrials.gov ID: NCT06043674
What this study is testing
What is Glofitamab?
an investigational intravenous bispecific antibody being studied as a potential treatment for Richter's Transformation of chronic lymphocytic leukemia is designed to bind CD20 on cancer B‑cells and CD3 on T‑cells, bringing T‑cells close to the cancer cells to trigger an immune attack
Also referred to as RO7082859.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The study aims to find out if Glofitamab, by itself or combined with Polatuzumab vedotin, Pirtobrutinib, or Atezolizumab, is safe and shows activity against Richter's transformation.
- Who it's for
- Adults who have chronic lymphocytic leukemia that has changed into Richter's transformation.
- What's involved
- Participants receive intravenous infusions of Glofitamab alone or together with the other study drugs, plus regular clinic visits for exams, blood tests, and imaging.
- Phase 2: a mid-size study of how well it works
- Time commitment: about 10 years
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as per IW-CLL 2018 criteria with biopsy proven...
- 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...
- Glofitamab monotherapy cohort: Patients with either relapsed/refractory or previously untreated Richter's Transformation.
- Glofitamab + polatuzumab vedotin cohort: Patients with previously untreated RT.
You likely can't join if
- CLL/SLL
- Malignancy treated with curative intent and with no known active disease present before the first dose of study drug and felt to be at low risk for...
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- Low-risk prostate cancer on active surveillance For patients receiving polatuzumab vedotin: Current \> Grade 2 peripheral neuropathy.
- Patients with a remote history of, or well controlled, autoimmune disease may be eligible to enroll after consultation with the study PI.
See the full eligibility criteria
Who can join
- 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...
- 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...
- 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...
- Glofitamab + pirtobrutinib cohort: Patients with previously untreated RT and prior BTK inhibitor exposure (with enrollment to begin only after the first 10 patients are accrued to the polatuzumab combination cohort).
- Absolute neutrophil count must be \> 1.0 x109/L (growth factor allowed to achieve), unless patients have significant bone marrow involvement of their malignancy confirmed on biopsy.
- Platelets must be \> 30 x109/L, independent of transfusion within 7 days of screening, unless patients have bone marrow involvement of their malignancy confirmed on biopsy
- Creatinine \ 50 ml/min according to Cockcroft/Gault formula
- Total bilirubin \< 1.5 X ULN o people with Gilbert's Syndrome or resolving autoimmune hemolytic anemia may have a bilirubin up to 3.0 X ULN
- Absolute neutrophil count must be \> 1.0 x109/L (growth factor \>7 days prior allowed to achieve), unless patients have significant bone marrow involvement of their malignancy confirmed on biopsy.
- Hemoglobin \> 8 g/dL, independent of transfusion within 7 days of screening, unless patients have bone marrow involvement of their malignancy confirmed on biopsy
- Platelets must be \> 50 x109/L, independent of transfusion within 7 days of screening
- Estimated CrCl \> 50 ml/min according to Cockcroft/Gault formula
- AST/ALT \< 3.0 X ULN, or \< 5.0 X ULN with documented liver involvement by lymphoma
- Total bilirubin \< 1.5 X ULN or \< 3.0 x ULN with documented liver involvement by lymphoma and/or Gilbert's Disease
- Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x ULN.
- No current or prior Grade 3/4 graft versus host disease (GVHD)
- No active/current GVHD
- No prior history of Grade 3/4 GVHD
- Female patients: at least 18 months after pre-treatment with obinutuzumab, or 2 months after the last dose of glofitamab, or 5 months after the last dose of atezolizumab, or 9 months after the last dose of polatuzumab...
- Male patients: at least 6 months after pre-treatment with obinutuzumab, or 2 months after the last dose of glofitamab, or 6 months after the last dose of polatuzumab vedotin, or 2 months after the last dose of...
- Examples of highly effective contraceptive methods with a failure rate of \<1% per year include: Tubal ligation, male sterilization, hormonal implants, established proper use of hormonal contraceptives that inhibit...
What rules you out
- CLL/SLL
- Malignancy treated with curative intent and with no known active disease present before the first dose of study drug and felt to be at low risk for recurrence by treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- Low-risk prostate cancer on active surveillance For patients receiving polatuzumab vedotin: Current \> Grade 2 peripheral neuropathy.
- Patients with a remote history of, or well controlled, autoimmune disease may be eligible to enroll after consultation with the study PI.
- Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone and patients with controlled Type 1 diabetes mellitus who are on an insulin regimen can be included.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided that the disease is...
- For patients enrolling to the pirtobrutinib combination arm, patients with the following will be excluded: active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic...
- Note the following are permitted: use of inhaled corticosteroids, use of mineralocorticoids for management of orthostatic hypotension.
- For patients receiving glofitamab in combination with pirtobrutinib, patients who have tested positive for HIV are excluded due to risk of opportunistic infections with both HIV and BTK inhibitors.
- unstable angina or acute coronary syndrome within the past 2 months prior to randomization
- history of myocardial infarction within 3 months prior to randomization or
- documented LVEF by any method of ≤ 40% in the 12 months prior to randomization
- Uncontrolled or symptomatic arrhythmias
- Note: patients with atrial fibrillation are allowed as long as they are adequately rate-controlled.)
- Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
- Prolongation of the QT interval corrected for heart rate (QTcF) \> 470 msec. QTcF is calculated using Fridericia's Formula (QTcF): QTcF = QT/(RR0.33).
- Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug...
- Correction for underlying bundle branch block (BBB) allowed.
- Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug.
- Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) for which new therapy was introduced or existing therapy was escalated within the 4 weeks...
- Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.
- Have a known hypersensitivity to any of the excipients of Pirtobrutinib or to any intended study medications.
- Patients who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor.
- History of bleeding disorders (e.g. von Willebrand's disease, hemophilia).
- History of stroke or intracranial hemorrhage within 6 months of starting study therapy. Inability to comply with protocol mandated hospitalizations and restrictions.
The study team makes the final eligibility decision.
Where it is enrolling
- Atlanta, Georgia, United States
- Boston, Massachusetts, United States
- Chapel Hill, North Carolina, United States
- Columbus, Ohio, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The study runs about 10 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Atlanta, Georgia, United States; Boston, Massachusetts, United States; Chapel Hill, North Carolina, United States; Columbus, Ohio, United States. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.