A Phase 2 Study of Acalabrutinib in Combination With Lisocabtagene Maraleucel in Relapsed/Refractory Aggressive B-cell Lymphomas
概览
- 阶段
- 2 期
- 干预措施
- ACALABRUTINIB
- 疾病 / 适应症
- Refractory Aggressive B-cell Lymphomas
- 发起方
- Patrick C. Johnson, MD
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Complete Response Rate (CRR)
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
This research is being done to assess the effectiveness and safety of acalabrutinib combined with lisocabtagene maraleucel (liso-cel) for people with relapsed/refractory aggressive B-cell lymphoma.
This research study involves the study drug acalabrutinib in combination with lisocabtagene maraleuce
详细描述
This research study involves the study drug acalabrutinib in combination with lisocabtagene maraleucel. The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. \- Participants will receive one infusion of liso-cel and will receive acalabrutinib capsules twice daily as long as treatment is tolerated and disease does not worsen (disease progression) for up to one year. Participants will be followed by clinical visits for up to 5 years and the medical record will be monitored for up to 15 years. It is expected that about 27 people will take part in this research study. This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The U.S. Food and Drug Administration (FDA) has not approved acalabrutinib for this specific disease, but it has been approved for other uses. The U.S. FDA has approved lisocabtagene maraleucel for this specific disease. AstraZeneca, a pharmaceutical company, is supporting this research study by providing funding for the research study and supplying acalabrutinib.
研究者
Patrick C. Johnson, MD
Sponsor Investigator
Massachusetts General Hospital
入排标准
入选标准
- •Adult patients ≥18 years with histologically confirmed aggressive B-cell NHL including diffuse large B-cell lymphoma (DLBCL), either de novo or transformed from any indolent B-cell lymphoma, and including DLBCL NOS, T cell/histiocyte-rich large B-cell lymphoma, Epstein-Barr virus \[EBV\] positive DLBCL NOS, primary mediastinal \[thymic\] large B-cell lymphoma (PMBCL), high grade B-cell lymphoma NOS, or high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements \[double/triple hit lymphoma (DHL/THL)\]; and grade 3B follicular lymphoma. Patients with primary CNS lymphoma are not eligible. Patients with secondary CNS involvement by lymphoma are eligible if they otherwise meet all eligibility criteria.
- •Relapsed or refractory to at least 2 prior lines of systemic lymphoma therapy. Previous therapy must have included a CD20-targeted agent and an anthracycline or alkylating agent.
- •PET-positive measurable disease
- •ECOG Performance status 0-2
- •Estimated creatinine clearance of ≥30 mL/min, calculated using the Cockcroft and Gault equation (if male, \[140Age\] x Mass \[kg\] / \[72 x creatinine g/dL\];multiply by 0.85 if female)
- •Alanine Aminotransferase (ALT) \<= 2.5 times the ULN
- •Bilirubin \<= 2 x ULN (or \<= 3.0 mg/dL for patients with Gilbert-Meulengracht syndrome or lymphomatous involvement of the liver)
- •Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) \>= 40% confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA)
- •For subjects with atrial fibrillation, atrial fibrillation must be controlled and asymptomatic
- •Absolute neutrophil count (ANC) \>= 1000/mm3
排除标准
- •Another active malignancy which requires concurrent cancer-directed therapy
- •Previous treatment with gene therapy product or adoptive T cell therapy
- •Allogeneic stem cell transplant within 90 days of leukapheresis
- •Active acute or chronic GVHD
- •HIV infection
- •Serologic status reflecting active hepatitis B or C infection
- •Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before enrollment and must be willing to undergo DNA PCR testing during the study. Those who are HbsAg-positive or hepatitis B PCR positive will be excluded.
- •Subjects who are hepatitis C antibody positive will need to have a negative PCR result before enrollment. Those who are hepatitis C PCR positive will be excluded.
- •Uncontrolled infection
- •Clinically relevant CNS pathology
研究组 & 干预措施
ACALABRUTINIB and LISOCABTAGENE MARALEUCEL
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits, as tolerated for one year * Liso-cel * Acalabrutinib
干预措施: ACALABRUTINIB
ACALABRUTINIB and LISOCABTAGENE MARALEUCEL
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits, as tolerated for one year * Liso-cel * Acalabrutinib
干预措施: LISOCABTAGENE MARALEUCEL
ACALABRUTINIB and LISOCABTAGENE MARALEUCEL
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits, as tolerated for one year * Liso-cel * Acalabrutinib
干预措施: Lymphodepleting chemotherapy
结局指标
主要结局
Complete Response Rate (CRR)
时间窗: 1 year 8 months
The CRR is defined as the percentage of subjects achieving an objective response of complete response (CR) according to the Lugano Classification (Chesson et al., 2014), prior to start of another non-study anticancer therapy. CR is defined as a complete metabolic and radiologic response (Lugano score 1-3, target nodes/nodal masses must regress to ≤ 1.5 cm in longest diameter.)
次要结局
- Overall Survival(defined as the time from registration to death due to any cause, or censored at date last known alive up to 15 years)
- Duration of Response(time from first response to disease progression or death up to 15 years)
- Overall Response Rate(12 Months)
- Progression Free Survival(as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation up to 15 years)
- ICU Rates(up to 90 days)
- FACT-G QOL(baseline, day -5 (+/- 3 days), day +7 (+/- 3 days), day +30 (+/- 7 days), day +90 (+/- 14 days), and day +180 (+/- 14 days) after liso-cel infusion)
- Length of Stay(1 year)
- Overall Response Rate(3 Months)
- Overall Response Rate(6 Months)
- Event Free Survival(from registration to death from any cause, disease progression, or starting a new anti-lymphoma therapy, whichever occurs first up to 15 years)
- Rates of Bridging Therapy(1 years)
- Re-hospitalization Rates(up to 90 days)
- ER Visit Rates(within 90 days)
- Rates of Acalabrutinib Discontinuation Due to Toxicity(time of their first treatment up to 3 years)
- Number of Participants Treatment Related Adverse Event NCI CTCAE 5.0(up to 3 Years)