A Pilot Study of Blinatumomab in Combination With a PD1 Inhibitor, Pembrolizumab, in Pediatric and Young Adult Patients With Relapsed/Refractory CD19 Positive B-cell Acute Leukemia or Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Treatment related toxicities
研究概览
简要总结
This study combines the immune checkpoint inhibitor pembrolizumab with the BITE antibody blinatumomab for the treatment of relapsed/refractory pre-B cell ALL. Pembrolizumab at the proposed dosing schedule has been very well tolerated in adult studies, including elderly and unfit patients, as well as in pediatric patients. Both blinatumomab and pembrolizumab are FDA-approved for use in children as well as adults. Phase I/II trials in adult patients have demonstrated safety and activity of pembrolizumab in combination with multiple agents. In this trial, the combination of pembrolizumab and blinatumomab will be investigated for toxicity as well as possible synergy in the treatment of relapsed/refractory pre-B cell ALL.
This is a single institution investigator-initiated pilot study designed to test the safety and feasibility of combining pembrolizumab and blinatumomab immunotherapies in children, adolescents, and young adults with CD19 positive hematologic malignancies. The investigator will define the toxicity profile of the combination in two safety strata based on whether or not a patient has had a prior allogeneic hematopoietic stem cell transplant (HSCT), as they hypothesize that the immune toxicities may differ between strata. In addition, the overall response rate (CR/CRh) to this therapy will be estimated. Additional biologic correlates will be conducted to delineate the effect of the combination therapy on the patient's leukemia/lymphoma and T-cell populations and how this may influence response to therapy.
详细描述
Participants who meet study eligibility will receive or continue to receive blinatumomab by continuous IV infusion for 28 days and also receive pembrolizumab (by IV infusion over 30 minutes) on day 12 of cycle 1 and day 5 of cycle 2.
One cycle lasts 35 days and patients will receive 2 cycles of therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of CD19 positive B-cell acute lymphoblastic leukemia (ALL) positive B-cell acute lymphoblastic leukemia (ALL) or CD19 positive B-cell lymphoma
- •Patients with CD19 positive B-ALL must have greater than or equal to 5% lymphoblast in the bone marrow AND meet one of the following criteria:
- •2nd or greater relapse
- •Any relapse after allo-HSCT
- •Refractory disease
- •Patients with CD19 positive relapsed/refractory lymphoma must be in 2nd or greater relapse or have refractory disease with the markers of disease burden
- •Patients with CNS 1 or CNS 2 leukemia are eligible.Patients with CNS 3 leukemia are not eligible. However, patients with a history of CNS 3 status who have been sufficiently treated are eligible if currently CNS 1 or
- •Patients with an isolated CNS relapse are not eligible.
- •Karnofsky performance level greater than or equal to 50 % for patients older than 16
- •Lansky performance level greater than or equal to 50 % less than or equal to 16
- •Patients recovered from acute toxicities from prior anti-cancer chemotherapy including HSCT, cytotoxic therapy, prior blinatumomab, biologic, immunotherapy, monoclonal antibody, XRT and corticosteroid therapy
- •Patients with adequate hematological, renal, liver, cardiac, pulmonary and CNS organ functions
- •Female participants of child bearing age must have negative pregnancy test, abstain or use contraception for 120 days after last dose of pembrolizumab
排除标准
- •Patients with the following diagnoses: CNS 3 leukemia, CNS lymphoma, active GVHD, Downs Syndrome, CNS or testicular relapse, optic nerve or retinal involvement requiring radiation therapy
- •Pregnant or breastfeeding
- •Concomitant corticosteroids, immunosuppressive therapies, investigational drugs, anti-cancer agents
- •Concurrent illnesses including: history of any grade autoimmune disorder, Grade 2 or higher hypothyroidism die to autoimmunity, uncontrolled infection, interstitial lung disease or pneumonitis
- •Patients with other concurrent malignancies
- •Patients who have received live vaccines within the last 30 days
- •Patients with history of solid organ transplant
研究组 & 干预措施
Blinatumomab and Pembrolizumab
Blinatumomab and Pembrolizumab will be given for 2 cycles (each cycle lasts 35 days).
Blinatumomab administered as a continuous IV infusion. Patient Weight Greater Than or Equal to 45 kg (Fixed dose) Patient Weight Less Than 45 kg (BSA-based dose)
Cycle 1 (Days 1-7):
Patient Weight Greater Than or Equal to 45 kg: 9 mcg/day Patient Weight Less Than 45 kg: 5 mcg/m2/day
Cycle 1(Days 8-28):
Patient Weight Greater Than or Equal to 45 kg: 28 mcg/day Patient Weight Less Than 45 kg: 15 mcg/m2/day
Cycle 2 (Days 1-28):
Patient Weight Greater Than or Equal to 45 kg: 28 mcg/day Patient Weight Less Than 45 kg: 15 mcg/m2/day
Pembrolizumab: 2 mg/kg (max dose 200 mg) administered as a 30 minute IV infusion on day 12 of cycle 1 and day 5 of cycle 2.
干预措施: Blinatumomab (Drug)
Blinatumomab and Pembrolizumab
Blinatumomab and Pembrolizumab will be given for 2 cycles (each cycle lasts 35 days).
Blinatumomab administered as a continuous IV infusion. Patient Weight Greater Than or Equal to 45 kg (Fixed dose) Patient Weight Less Than 45 kg (BSA-based dose)
Cycle 1 (Days 1-7):
Patient Weight Greater Than or Equal to 45 kg: 9 mcg/day Patient Weight Less Than 45 kg: 5 mcg/m2/day
Cycle 1(Days 8-28):
Patient Weight Greater Than or Equal to 45 kg: 28 mcg/day Patient Weight Less Than 45 kg: 15 mcg/m2/day
Cycle 2 (Days 1-28):
Patient Weight Greater Than or Equal to 45 kg: 28 mcg/day Patient Weight Less Than 45 kg: 15 mcg/m2/day
Pembrolizumab: 2 mg/kg (max dose 200 mg) administered as a 30 minute IV infusion on day 12 of cycle 1 and day 5 of cycle 2.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Treatment related toxicities
时间窗: 2 cycles of therapy (70 days)
Number of related adverse events
Feasibility of combining pembrolizumab and blinatumomab (dose limiting toxicities)
时间窗: 2 cycles of therapy (70 days)
Number of DLTs
次要结局
- Disease response(2 cycles (70 days))