Phase I Trial of Targeted Immunotherapy With Daratumumab Following Myeloablative TBI-Based Conditioning and AlloHCT in Children, Adolescents and Young Adults With High Risk T-Cell Acute Lymphoblastic Leukemia and Lymphoma (ALLO-T-DART)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 21
- 主要终点
- Patients with dose limiting toxicity (per CTCAE v.5)
研究概览
简要总结
A Phase I trial to determine the safety of targeted immunotherapy with daratumumab (DARA) IV after total body irradiation (TBI)-based myeloablative conditioning and allogeneic hematopoietic cell transplantation (HCT) for children, adolescents, and young adults (CAYA) with high risk T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LLy).
Pre- and post-HCT NGS-MRD studies will be correlated with outcomes in children, adolescents, and young adults with T-ALL undergoing allogeneic HCT and post-HCT DARA treatment. The study will also evaluate T-cell repertoire and immune reconstitution prior to and following DARA post-HCT treatment and correlate with patient outcomes.
详细描述
Total body irradiation (TBI)-based myeloablative allogeneic hematopoietic stem cell transplantation (HCT) using best available donor.
Daratumumab (DARA) treatment post-HCT:
Phase 1: 3 dose levels to determine safety (15 patients)
Dose expansion cohort (DEC): Further evaluation of PK and PD (correlative studies/exploratory endpoints) to guide future selection of RP2D (15 patients)
Treatment Schedule:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 39 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •T-cell ALL in second or subsequent remission (≤ 5% blasts) or relapsed T-cell LLy with complete response after re-induction therapy (including secondary malignancy)
- •Planned allogeneic stem cell transplantation with donor identified
- •Performance status ≥ 60%
- •Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- •Meet organ function requirements
- •Signed IRB approved informed consent
排除标准
- •May not have had a prior autologous or allogenic stem cell transplant
- •May not have uncontrolled, systemic infection at the time of enrollment
- •Known allergies, hypersensitivity, or intolerance to mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients
- •Must not be pregnant or actively breast feeding
- •Seropositive for HIV, hepatitis B or hepatitis C
- •Clinically significant cardiac disease
研究组 & 干预措施
Interventional
Phase 1: 3 dose levels to determine safety (15 patients)
Dose expansion:
Daratumumab (DARA) treatment post-HCT
- Induction: DARA IV weekly x 8 doses (Weeks 1-8)
- Consolidation: DARA IV every 2 weeks x 8 doses (Weeks 9-24)
- Maintenance: DARA IV every 4 weeks (Stop at Day +270)
干预措施: Daratumumab (Drug)
结局指标
主要结局
Patients with dose limiting toxicity (per CTCAE v.5)
时间窗: 60 days
occurrence of any Grade ≥ 3 non hematologic toxicity (per CTCAE v.5) which is probably, or definitely related to daratumumab
次要结局
- Relapse free survival(1 year)