March 22, 2023
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April 5, 2023
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February 23, 2024
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April 6, 2023
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September 15, 2026 (Final data collection date for primary outcome measure)
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Complete Response (CR) Rate [ Time Frame: Baseline through 28 days post Cycle 8 of Glofitamab (each cycle is 21 days) ] The complete response (CR) Rate is the proportion of participants achieving CR based on Lugano criteria defined per protocol section 11.1.1 for target lesions.
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Same as current
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- Dose-Limiting Toxicity (DLT) [ Time Frame: 42 days ]
A DLT will be defined as any of the adverse events (AE) in protocol section 5.4.1 defined toxicities that are determined to be at least possibly related to glofitamab-pola-R-CHP.
- Grade 3-5 Treatment-related Toxicity Rate [ Time Frame: Up to 9 months ]
All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 AE of any type during the time of observation.
- Overall Response Rate (ORR) [ Time Frame: 8 months ]
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on criteria defined per protocol section 11.1.1.
- Median Duration of Response (DOR) [ Time Frame: Up to 24 months ]
Duration of Overall Response (DOR), estimated using the Kaplan Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) per protocol defined section 11.1.1, until the first date that recurrent or progressive disease is objectively documented. Patients without progressive disease are censored at the date of last disease assessment.
- Median Progression-Free Survival (PFS) [ Time Frame: Up to 24 months ]
Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) per Lugano criteria or death, or is censored at time of last disease assessment.
- 1-Year Progression Free Survival rate [ Time Frame: 1 year ]
1-year PFS rate is the proportion of participants remaining alive and progression free at 1 year. Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. PD is defined per Lugano 2014 criteria.
- Median Overall Survival (OS) [ Time Frame: up to 5 years ]
Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
- Change in ctDNA level from Baseline to 2 cycles by Objective Response Status or PFS or OS [ Time Frame: Baseline and end of cycle 2 (each cycle is 21 days) ]
ctDNA will be measured using the Avenio assay.
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Same as current
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Not Provided
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Not Provided
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A Phase II Study of Glofitamab Plus Polatuzumab-R-CHP for Patients With High-risk Diffuse Large B-cell Lymphoma
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A Phase II Study of Glofitamab Plus Polatuzumab-R-CHP for Patients With High-risk Diffuse Large B-cell Lymphoma
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The goal of this research study is to evaluate the combination of study drugs, Glofitamab and Polatuzumab, and a standard chemotherapy regimen, R-CHP, as a treatment for high-risk diffuse large B-cell lymphoma.
The names of the treatment interventions involved in this study are:
- Glofitamab (T-cell bispecific antibody)
- Polatuzumab (antibody-drug conjugate)
- R-CHP (a chemotherapy regimen comprised of Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, and Prednisone)
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This study is an open-label, multi-center, single-arm phase II study of glofitamab plus polatuzumab and R-CHP for patients with previously untreated high-risk diffuse large B-cell lymphoma (DLBCL).
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Study procedures include screening for eligibility, study evaluations, radiological scans of tumors, tumor biopsies, TTE/MUGA scans, and blood collections.
- All participants will receive two cycles of polatuzumab -R-CHP and four cycles of glofitamab- polatuzumab -R-CHP. After completion of chemotherapy patients will receive two additional cycles of glofitamab alone.
- Participants receive study treatment for up to 8 cycles of treatment and will be followed for 5 years.
- It is expected that about 40 people will take part in this research study.
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This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
- The U.S. Food and Drug Administration (FDA) has not approved glofitamab as a treatment for any disease.
- The FDA has approved polatuzumab in combination with rituximab and another chemotherapy agent, bendamustine, for DLBCL that has already been treated with two prior treatments, but not as an initial therapy.
- The R-CHP regimen is FDA approved and standard care for cancer treatment.
- Genentech is supporting this research study by providing drug and funding for this trial.
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Interventional
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Phase 2
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Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Lymphoma
- Lymphoma, Large B-Cell, Diffuse
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- Drug: Glofitamab
human IgG1-bispecific antibody, via IV infusion
Other Name: RO7082859
- Drug: Polatuzumab
an antibody drug conjugate (ADC) that contains a humanized IgG1 anti-human CD79b monoclonal antibody, via IV infusion
Other Name: Polatuzumab vedotin, DCDS4501S, RG7596
- Drug: Rituximab
Per standard care, via IV infusion
Other Name: Rituxan
- Drug: Doxorubicin Hydrochloride
Per standard care, via IV infusion
Other Name: Hydroxydaunomycin
- Drug: Cyclophosphamide
Per standard care, via IV infusion
Other Name: Cytophosphane, Cytoxan
- Drug: Prednisone
Per standard care, orally
Other Name: Prednisolone, Methylprednisolone
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Experimental: Polatuzumab + Glofitamab + R-CH
-Participants will receive treatment interventions as outlined: Experimental: Safety Lead-In Phase of 6 Participants, Total Enrollment of 40 Participants
Interventions:
- Drug: Glofitamab
- Drug: Polatuzumab
- Drug: Rituximab
- Drug: Doxorubicin Hydrochloride
- Drug: Cyclophosphamide
- Drug: Prednisone
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Not Provided
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Recruiting
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40
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Same as current
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September 15, 2029
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September 15, 2026 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
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Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses by 2016 WHO classification of lymphoid neoplasms
- DLBCL, not otherwise specified (NOS)
- T-cell/histiocyte-rich large B-cell lymphoma
- Epstein-Barr virus-positive DLBCL, NOS
- ALK-positive large B-cell lymphoma
- HHV8-positive DLBCL, NOS
- High-grade B-cell lymphoma (HGBCL), NOS
- HGBCL with translocations of MYC and BCL-2, or MYC and BCL-6
- Availability of archival (within 90 days) or freshly collected tumor tissue before study enrollment. If archival tissue is unavailable or is determined to be inadequate, tumor tissue must be obtained from a biopsy performed at screening, unless an exception is given after consultation with the principal investigator.
- IPI score of 2-5
- ECOG Performance Status of 0, 1, or 2 (see Appendix A)
- Greater than or equal to 18 years at the time of signing informed consent
- Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
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Adequate hematologic function (unless due to underlying disease, as established for example, by extensive bone marrow involvement or due to hypersplenism secondary to the involvement of the spleen by DLBCL per the investigator), defined as follows:
- Hemoglobin ≥ 9.0 g/dL without transfusion for 14 days before first treatment
- ANC ≥ 1,000/μL
- Platelet count ≥ 75,000/μL
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Participants must have adequate organ as defined below:
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) or < 3 x ULN in participants with Gilbert's disease
- PT or INR > 1.5 the ULN in the absence of therapeutic anticoagulation or lupus anticoagulant
- AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN
- Adequate renal function defined by serum creatinine ≤1.5 x ULN or creatinine clearance (by Cockcroft-Gault) ≥ 40 ml/min
- At least one bi-dimensionally FDG-avid measurable lymphoma lesion on PET/CT scan, defined as > 1.5 cm in its longest dimension on CT scan
- Women of childbearing potential (WOCBP) must agree to use effective contraception when sexually active. Women must remain abstinent or use methods of contraception, including at least one method with a failure rate of <1% per year, during the treatment period and for 12 months after the final dose of pola-R-CHP, 2 months after the last dose of glofitamab, and 9 months after the last dose of polatuzumab whichever is longer. Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control. The use of condoms by male patients is required unless the female partner is permanently sterile.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 12 months after the final dose of pola-R-CHP, 2 months after the last dose of glofitamab, and 9 months after the last dose of polatuzumab whichever is longer. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Male patients considering preservation of fertility should bank sperm before study treatment.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients must be willing to have monthly testing and antiviral therapy if indicated. Participants with a history of hepatitis C virus (HCV) infection must have undetectable viral load.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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United States
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NCT05800366
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22-606
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research. |
Supporting Materials: |
Study Protocol |
Supporting Materials: |
Statistical Analysis Plan (SAP) |
Time Frame: |
Data can be shared no earlier than 1 year following the date of publication. |
Access Criteria: |
Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu |
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Jennifer Crombie, MD, Dana-Farber Cancer Institute
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Philippe Armand, MD, PhD, Dana-Farber Cancer Institute, Principal Investigator
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Jennifer Crombie, MD
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Philippe Armand, MD, PhD
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Genentech, Inc.
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Principal Investigator: |
Jennifer Crombie, MD |
Dana-Farber Cancer Institute |
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Dana-Farber Cancer Institute
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February 2024
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