Safety and Efficacy Study of PD-616 Plus Cytarabine to Treat Acute Myelogenous Leukemia or Myelodysplastic Syndrome (AML/MDS)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01795924|
Recruitment Status : Terminated (Difficulty of patient enrollment)
First Posted : February 21, 2013
Last Update Posted : July 24, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Myelogenous Leukemia Myelodysplastic Syndrome||Drug: PD-616||Phase 1 Phase 2|
Protocol RT12-US-AML-a is a 2-part, Phase 1/2, multi-center, open-label, dose-escalation study of PD-616 in combination with low-dose cytarabine in patients with AML or high-risk MDS not eligible for standard therapy.
Part 1 of this study (Phase 1 portion) employs a sequential group-dose escalation design to determine the DLT and MTD of PD-616 in combination with low-dose cytarabine (primary objective). The safety and PK profiles as well as the preliminary efficacy of PD-616 in combination with cytarabine also will be examined (secondary objectives). Approximately 21 patients are planned to be enrolled in Part 1.
After provision of written informed consent, patients are to be evaluated for study eligibility during the Screening period which should be within 14 days before the first day of study drug administration (Cycle 1, Day 1 [C1D1]; Baseline). Patients who are determined to be eligible, based on Screening assessments, will be enrolled in the study on C1D1, which is the first day of study drug administration.
Part 2 of this study (Phase 2 portion) will commence with approval of the Safety Review Committee (SRC) after identification of the MTD, or if the MTD is not established, the maximum feasible dose has been evaluated in Part 1. Twelve additional patients will be enrolled and treated with PD-616 at the MTD (or other biologically relevant dose) in combination with low-dose cytarabine according to the same schedule as in Part 1. The safety profile, PK, and efficacy of the study drug combination will be further investigated in Part 2 of this study.
Each cycle of treatment consists of a treatment period (D1 through D12) and a rest period (D13 through D28). During the treatment period, patients are required to return to the study center on D1 through D5 and D8 through D12 for study drug to be administered and evaluations to be performed. During the rest period, patients are required to return to the study center at least once a week for study evaluations. In addition, patients are required to be evaluated for peripheral blasts by flow cytometry in the last week of each cycle (D22 to D28) and to receive bone marrow examination in the last week (D22 to D28) of C1. Patients with evidence of complete response (CR) in peripheral blood by flow cytometry are to have a repeat bone marrow examination performed to confirm CR.
All patients are to attend the Study Drug Discontinuation Visit within 3 days after discontinuing study drug. Thereafter, patients will enter the post-study period and be followed monthly (±3 days), starting 30±3 days after last study drug administration, through 1 year post-C1D1. During the post-study period, patients who discontinue for reasons other than progressive disease (PD) also will have follow-up blood samples collected for evaluation of changes in the percentage of blasts every month until PD or receipt of alternative therapy, whichever occurs first, up to 1 year post-C1D1. During the post-study period, patients with evidence of CR in peripheral blood by flow cytometry are to have a repeat bone marrow examination performed to confirm CR.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label, Phase 1/2 Study of PD-616 and Low-dose Cytarabine in Patients With Untreated or Relapsed/Refractory Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)|
|Actual Study Start Date :||January 2013|
|Actual Primary Completion Date :||September 2014|
|Actual Study Completion Date :||November 2014|
Experimental: PD-616 plus low-dose Cytarabine
Patients will receive low-dose cytarabine (20 mg/m2) subcutaneously (SC) once daily (QD), followed by a 1-hour intravenous (IV) infusion of PD-616 for 5 consecutive days during Week 1 (D1 to D5) and Week 2 (D8 to D12) of a 28-day treatment cycle. Cytarabine is to be administered approximately 30 minutes before PD-616. In Phase 1 part, the starting dose of PD-616 is 0.0875 mg/m2, with sequential increments of 0.0375 mg/m2, to 0.125, and 0.1625 mg/m2. The dose of PD-616 to be administered in Phase 2 part will be the maximum tolerated dose (MTD)determined from Phase 1 part of the study.
Patients may continue treatment through 1 year post-C1D1 or until withdrawal of consent or development of any toxicity meeting the definition of Dose-Limiting Toxicity or progressive disease, whichever occurs first.
- The number of dose-limiting toxicities in each cohort of PD-616 in combination of low-dose Cytarabine to determine the maximum tolerated dose of PD-616. [ Time Frame: Average 28 days after the first dose of treatment ]Primary outcome measure for the Phase 1 part of the study.
- The percentage of patients achieving complete or partial remission after the treatment of PD-616 at the maximum tolerated dose in combination with low-dose Cytarabine. [ Time Frame: One year from the first dose of treatment ]Primary outcome measure for Phase 2 part of the study.
- The pharmacokinetic profile of PD-616 consisting AUC. [ Time Frame: 1 hour before and 20, 40 and 60 minutes during and 0.5, 1, 2, 4, 6, 10 hours after treatment on Day 1 and Day 5 and before treatment on Day 2, Day 3 and Day 4 ]
- The pharmacokinetic profile of PD-616 consisting Cmax. [ Time Frame: 1 hour before and 20, 40 and 60 minutes during and 0.5, 1, 2, 4, 6, 10 hours after treatment on Day 1 and Day 5 and before treatment on Day 2, Day 3 and Day 4 ]
- The pharmacokinetic profile of PD-616 consisting Tmax. [ Time Frame: 1 hour before and 20, 40 and 60 minutes during and 0.5, 1, 2, 4, 6, 10 hours after treatment on Day 1 and Day 5 and before treatment on Day 2, Day 3 and Day 4 ]
- The pharmacokinetic profile of PD-616 consisting Cmin. [ Time Frame: 1 hour before and 20, 40 and 60 minutes during and 0.5, 1, 2, 4, 6, 10 hours after treatment on Day 1 and Day 5 and before treatment on Day 2, Day 3 and Day 4 ]
- The proportion of patients experiencing adverse events. [ Time Frame: One year from the first dose of treatment ]
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): NCT01795924
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|United States, Kentucky|
|University of Kentucky Medical Center|
|Lexington, Kentucky, United States, 40513|
|Principal Investigator:||Anthony S Stein, MD||City of Hope Medical Center|
|Principal Investigator:||Dianna S. Howard, M.D.||University of Kentucky|