High Dose Cytarabine Followed by Pembrolizumab in Relapsed/Refractory AML
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|ClinicalTrials.gov Identifier: NCT02768792|
Recruitment Status : Active, not recruiting
First Posted : May 11, 2016
Last Update Posted : September 4, 2019
Rationale:The purpose of this research study is to test the effectiveness of the standard high dose cytarabine (HiDAC) on days 1 through 5 followed by a single dose of pembrolizumab on day 14 as induction therapy in patients with relapsed and refractory acute myeloid leukemia (AML). Patients who achieve a response to treatment will continue on the study drug (pembrolizumab) every 3 weeks for up to 2 years maintenance therapy.
Purpose:This is a study about a new investigative drug, pembrolizumab (MK-3475) that is being studied in a clinical research trial together with standard chemotherapy (HiDAC) in relapsed and refractory AML. The study will also explore the association between potential immune biomarkers and clinical outcomes with pembrolizumab; therefore all patients will have blood and bone marrow samples collected before and after treatment to determine the dynamic nature of immune signatures pre and post-treatment.
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia, in Relapse||Drug: pembrolizumab,||Phase 2|
1. Estimate the objective overall rate of CR (CR+CRi) for age-adjusted HiDAC (age <60 years: 2 gm/m2 IV Q12hours days 1-5; age >60 years: 1.5 gm/m2 IV Q12hours days 1-5) followed by pembrolizumab 200 mg IV on day 14 in relapsed and refractory AML patients
- Estimate the rate of unacceptable toxicity associated with HiDAC followed by pembrolizumab as induction therapy
- Estimate the objective overall response rates (PR+CR+CRi) for HiDAC followed by pembrolizumab.
- Characterize the toxicity associated with HiDAC followed by pembrolizumab as induction therapy
- Characterize the toxicity associated with pembrolizumab 200 mg IV Q3weeks when used as monotherapy maintenance after an initial response to induction phase HiDAC followed by pembrolizumab
- Estimate the relapse-free survival (RFS) and progression-free survival (PFS) of patients receiving maintenance pembrolizumab
- Estimate the overall survival (OS) of patients who received induction phase treatment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||LCCC 1522: Phase 2 Study of High Dose Cytarabine Followed by Pembrolizumab in Relapsed and Refractory Acute Myeloid Leukemia|
|Actual Study Start Date :||August 22, 2016|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||September 2025|
open-label, multicenter, single-arm
Pembrolizumab 200 mg is administered IV once as monotherapy, 14 days after the initiation of HiDAC salvage induction chemotherapy. Patients who have a response (i.e., PR/CR/CRi) to induction phase will receive maintenance pembrolizumab at 200 mg IV every 3 weeks for up to 2-years of maintenance therapy (i.e., beginning on day 1 of maintenance). Patients who are ineligible for pembrolizumab administration by day 21 will be removed from the study.
Pembrolizumab 200 mg is administered IV once as monotherapy, 14 days after the initiation of HiDAC salvage induction chemotherapy. Patients who have a response (i.e., PR/CR/CRi) to induction phase will receive maintenance pembrolizumab at 200 mg IV every 3 weeks for up to 2 years of maintenance therapy (i.e., beginning on day 1 of maintenance).
- The rate of CR for age-adjusted HiDAC followed by pembrolizumab 200mg on day 14. [ Time Frame: 45 days ]Estimate of the objective overall rate of CR (CR+CRi) for age-adjusted HiDAC. The rate of CR+CRi as defined by the International European LeukemiaNet Guidelines in AML.
- Rate of unacceptable toxicity [ Time Frame: Day 14 until 2 years complete on study treatment ]number of drug-related grade 3 non-hematologic toxicity (with exception of infusion reactions, rash, fever, infection, nausea, fatigue, and anorexia) persisting for >7 days with supportive care, or any drug-related non-hematologic grade >4 toxicity (excluding infection). Toxicity will be classified and graded according to National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 4.0
- objective overall response rates (partial remission + complete remission + complete remission with incomplete blood count recovery) for HiDAC followed by pembrolizumab [ Time Frame: 45 days ]PR+CR+CRi as determined by International European LeukemiaNet Guidelines in AML
- Relapse-free survival (RFS of patients receiving maintenance pembrolizumab [ Time Frame: 2 years ]RFS will be defined as time from day 1 of CR/CRi to relapse or death from any cause.
- Progression-free survival (PFS) of patients receiving maintenance pembrolizumab. [ Time Frame: 7 years ]PFS will be defined as time from day 1 of response (i.e., PR/CR/CRi) to progression or death from any cause.
- Overall survival (OS) of patients who received induction phase of treatment. [ Time Frame: 7 years ]OS is defined as time from day 1 of treatment until date of last known follow up or death of any cause
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): NCT02768792
|United States, Maryland|
|Johns Hopkins School of Medicine The Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21205|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599-7295|
|Principal Investigator:||Joshua F Zeidner, MD||Lineberger Comprehensive Cancer Center University of North Carolina|