Safety and Efficacy Study of PD-616 Plus Cytarabine to Treat Acute Myelogenous Leukemia or Myelodysplastic Syndrome

NCT01795924 | Terminated Phase 1 DMC

• 1 other identifier: RT12-US-AML-a
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Acute Myelogenous Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  One year from the first dose of treatment

Secondary Outcomes (5)

• The pharmacokinetic profile of PD-616 consisting AUC.

  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.

  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.

  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.

  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.

  One year from the first dose of treatment

Study Arms (1)

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.

Drug: PD-616

Interventions

PD-616 DRUG

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.

Also known as: TPA, 12-O-Tetra-Decanoyl-Phorbol-13-Acetate

PD-616 plus low-dose Cytarabine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Biosuccess Biotech Co., Ltd.: lead

Study Sites (2)

City of Hope

Duarte, California, 91010, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40513, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Anthony S Stein, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

• Dianna S. Howard, M.D.

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2013
• First Posted: February 21, 2013
• Study Start: January 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: November 1, 2014
• Last Updated: July 24, 2018

Record last verified: 2018-07

Locations

US (2)