Pembrolizumab and Blinatumomab in Treating Participants With Recurrent or Refractory Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT03512405|
Recruitment Status : Suspended (pending intrim analysis)
First Posted : April 30, 2018
Last Update Posted : January 26, 2021
|Condition or disease||Intervention/treatment||Phase|
|CD19 Positive Philadelphia Chromosome Positive Recurrent Acute Lymphoblastic Leukemia Refractory Acute Lymphoblastic Leukemia||Biological: Blinatumomab Other: Laboratory Biomarker Analysis Biological: Pembrolizumab||Phase 1 Phase 2|
I. Assess the safety and tolerability of combination immunotherapy with blinatumomab and pembrolizumab by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (Phase 1) II. Determine the recommended phase 2 schedule of combination immunotherapy with pembrolizumab and blinatumomab. (Phase 1) III. Evaluate the anti-leukemia activity of combination immunotherapy blinatumomab and pembrolizumab as assessed by overall response rate (complete response [CR] or CR with incomplete recovery [CRi]). (Phase 2)
I. Estimate time to response (CR or CRi) and response duration. (Phase 2) II. Estimate overall survival and event-free survival. (Phase 2) III. Determine the number and proportion of patients who underwent hematopoietic stem cell transplantation (HSCT) after treatment of pembrolizumab and blinatumomab. (Phase 2) IV. Determine the number and proportion of patients who receive pembrolizumab maintenance and the proportion continuing for up to 1 year. (Phase 2) V. Estimate the minimal residual disease rate. (Phase 2)
I. Explore evolution of T cell subsets at various points in treatment (T naive, T effector, T effector memory, T central memory, CD4, CD8). (Phase 2) II. Evaluate PD-L1 expression levels on acute lymphoblastic leukemia (ALL) blasts and blasts counts overtime. (Phase 2) III. Evaluate PD-1/PD-L1 expression on subsets of T cells. (Phase 2) IV. Evaluate the clonal evolution of leukemic blasts in response to treatment. (Phase 2)
Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 15 of cycle 1 and days 1 and 22 of cycles 2 -5, and blinatumomab IV on days 1-28. Treatment repeats every 35-42 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response have the option to receive blinatumomab IV for up to 4 additional cycles.
After completion of study treatment, participants are followed up at 30 days and then every 3 months for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2 Trial of Pembrolizumab in Combination With Blinatumomab in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia|
|Actual Study Start Date :||August 2, 2019|
|Estimated Primary Completion Date :||April 2022|
|Estimated Study Completion Date :||April 2022|
Experimental: Treatment (pembrolizumab, blinatumomab)
Participants receive pembrolizumab IV over 30 minutes on day 15 of course 1 and days 1 and 22 of courses 2 -4, and blinatumomab IV on days 1-28. Treatment repeats every 35-42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of toxicity (Phase 1) [ Time Frame: Up to 42 days ]Will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5
- Response (Phase 2) [ Time Frame: Up to 1 year ]Response will be defined as complete response (CR)/CR with incomplete hematologic recovery (CRi) based on the National Comprehensive Cancer Network guidelines on acute lymphoblastic leukemia version 1 2017 response criteria. Evaluated using Simon two-stage optimal design
- Incidence of adverse events [ Time Frame: Up to 1 year ]Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, probable association with the study treatment and reversibility or outcome. Baseline information (e.g. the extent/type of prior therapy).
- Duration of remission [ Time Frame: From the date of first documented response (CR/CRi) up to 1 year ]
- Time to response [ Time Frame: From date of first dose of study drug up to 1 year ]Will be estimated using the product-limit method of Kaplan and Meier.
- Overall survival [ Time Frame: From date of first dose of study drug up to 1 year ]Will be estimated using the product-limit method of Kaplan and Meier.
- Event-free survival [ Time Frame: From date of first dose of study drug up to 1 year ]Will be estimated using the product-limit method of Kaplan and Meier.
- Allogeneic stem cell transplantation (SCT) realization rate [ Time Frame: Up to 1 year ]Will be measured by number and proportion of patients who underwent SCT after treatment of pembrolizumab and blinatumomab
- Number and proportion of patients who start pembrolizumab maintenance [ Time Frame: Up to 1 year ]
- Number and proportion of patients who complete pembrolizumab maintenance [ Time Frame: Up to 1 year ]
- Minimal residual disease rate confirmed minimal residual disease [ Time Frame: Up to 1 year ]Will be measured by number and proportion of patients with CR who have confirmed minimal residual disease.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03512405
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|Principal Investigator:||Lihua Budde||City of Hope Medical Center|