Acute Myelogenous LeukemiaPhase 1/2AML/MDSNCT01795924
Safety and Efficacy Study of PD-616 Plus Cytarabine to Treat Acute Myelogenous Leukemia or Myelodysplastic Syndrome
A Phase 1/2 study testing PD-616 in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by Biosuccess Biotech Co., Ltd. at 2 sites in United States.
Trial summary
The purpose of this study is to determine whether PD-616 in combination with low-dose Cytarabine is safe and effective in the treatment of untreated or relapsed/refractory acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Myelogenous Leukemia, Myelodysplastic Syndrome
- What is being tested?
- PD-616
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2013to Nov 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has newly diagnosed AML and refuses or is not eligible for treatment with aggressive chemotherapy and/or SCT; OR AML and has relapsed or been refractory to prior therapy; OR High-risk MDS, defined as IPSS intermediate-2 (INT-2) or IPSS high-risk, and refuses or is not eligible for standard or aggressive chemotherapy and SCT or prior experimental therapies; OR High-risk MDS, defined as IPSS INT-2 or IPSS high risk, and has failed or been refractory to deoxyribonucleic acid (DNA) hypomethylating agents (azacitidine or decitabine), lenalidomide, standard/aggressive chemotherapy, SCT, or prior experimental therapies.
- Has a bone marrow examination performed within 14 days before baseline (C1D1).
- Has an ECOG performance status score of 0 to 2.
- Aged between 18 and 75 years, inclusive.
- Has a life expectancy of ≥3 months.
- Has the following laboratory parameters within 7 days before baseline (C1D1):Serum creatinine ≤2 mg/dL; Total bilirubin ≤2.0 mg/dL; Alanine transaminase (ALT) or aspartate transaminase (AST) <3.0×the upper limit of normal (ULN); Left ventricular ejection fraction (LVEF) >40%; Forced expiratory volume in 1 second (FEV1) >60% of predicted.
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- If a female of child-bearing potential, has a negative serum pregnancy test result within 14 days before baseline and agrees to abstain from heterosexual intercourse or use a barrier method for contraception from 14 days before baseline (C1D1) through 30 days after the last study drug dose.
- If male, agrees to use a latex condom during any sexual contact with a female of child-bearing potential.
- Able to understand and willing to provide written informed consent.
Who cannot join
- Has received prior treatment with PD-616 or low-dose cytarabine.
- Has received chemotherapy (except hydroxyurea), biological therapy, radiotherapy or investigational therapy within 4 weeks before baseline (C1D1).
- Has active central nervous system (CNS) involvement (documented by radiologic lesions and/or malignant cells in the cerebrospinal fluid [CSF]).
- Has acute promyelocytic leukemia (APL, FAB M3).
- Has another active systemic malignancy treated with chemotherapy within 12 months before baseline (C1D1).
- Has known human immunodeficiency virus (HIV) infection.
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- Has active graft-versus-host disease (GVHD).
- Has uncontrolled active infection of any kind. (Patients with infections controlled by active antibiotic treatment are eligible).
- Has significant renal or hepatic disease, uncontrolled or severe cardiovascular or pulmonary diseases, or other uncontrolled medical condition that, based on the Investigator's assessment, would compromise the patient's ability to tolerate study treatment or the assessment of treatment response.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
City of Hope
Duarte, California, 91010
University of Kentucky Medical Center
Lexington, Kentucky, 40513
About this study
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)
The purpose of this study is to determine whether PD-616 in combination with low-dose Cytarabine is safe and effective in the treatment of untreated or relapsed/refractory acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS).
Read the detailed description
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.
- Being tested
- PD-616
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-616Drug
Also called TPA, 12-O-Tetra-Decanoyl-Phorbol-13-Acetate
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.
| Study group | Role | What they receive |
|---|---|---|
| PD-616 plus low-dose Cytarabine | Experimental | 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. Receives: Drug: PD-616 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Primary outcome measure for the Phase 1 part of the study.
Measured: Average 28 days after the first dose of treatment
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.
Primary outcome measure for Phase 2 part of the study.
Measured: One year from the first dose of treatment
Secondary outcomes (5)
The pharmacokinetic profile of PD-616 consisting AUC.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: One year from the first dose of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2013 (estimated)
- Study startJan 2013
- Primary completionSep 2014
- Study completionNov 2014
Why it stopped: Difficulty of patient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biosuccess Biotech Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anthony S Stein, MD, Principal investigator, City of Hope Medical CenterDianna S. Howard, M.D., Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01795924
- Sponsor's protocol ID
- RT12-US-AML-a
- Acronym
- AML/MDS
- Status last verified
- Jul 2018
- First submitted
- 13 Feb 2013
- Last updated
- 24 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01795924
- Acronym / sponsor ID
- AML/MDS / RT12-US-AML-a
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty of patient enrollment
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Biosuccess Biotech Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Jan 2013 (actual)
- Primary completion
- Sep 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 21 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether PD-616 in combination with low-dose Cytarabine is safe and effective in the treatment of untreated or relapsed/refractory acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS).
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PD-616 plus low-dose Cytarabine | Experimental | Drug: PD-616Patients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient has newly diagnosed AML and refuses or is not eligible for treatment with aggressive chemotherapy and/or SCT; OR AML and has relapsed or been refractory to prior therapy; OR High-risk MDS, defined as IPSS intermediate-2 (INT-2) or IPSS high-risk, and refuses or is not eligible for standard or aggressive chemotherapy and SCT or prior experimental therapies; OR High-risk MDS, defined as IPSS INT-2 or IPSS high risk, and has failed or been refractory to deoxyribonucleic acid (DNA) hypomethylating agents (azacitidine or decitabine), lenalidomide, standard/aggressive chemotherapy, SCT, or prior experimental therapies.
- Has a bone marrow examination performed within 14 days before baseline (C1D1).
- Has an ECOG performance status score of 0 to 2.
- Aged between 18 and 75 years, inclusive.
- Has a life expectancy of ≥3 months.
Key exclusion criteria (9 listed)
- Has received prior treatment with PD-616 or low-dose cytarabine.
- Has received chemotherapy (except hydroxyurea), biological therapy, radiotherapy or investigational therapy within 4 weeks before baseline (C1D1).
- Has active central nervous system (CNS) involvement (documented by radiologic lesions and/or malignant cells in the cerebrospinal fluid [CSF]).
- Has acute promyelocytic leukemia (APL, FAB M3).
- Has another active systemic malignancy treated with chemotherapy within 12 months before baseline (C1D1).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-616Also: TPA, 12-O-Tetra-Decanoyl-Phorbol-13-AcetatePatients 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. | Drug | PD-616 plus low-dose Cytarabine |
Primary outcome
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.
5 secondary outcomes
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
Results and safety
The study was stopped early (reason given: Difficulty of patient enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony S Stein, MD principal investigator
City of Hope Medical Center
Dianna S. Howard, M.D. principal investigator
University of Kentucky
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PD-616 in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by Biosuccess Biotech Co., Ltd. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulty of patient enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2018.