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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)


Phase 1/Phase 2
18 Years
75 Years
Open (Enrolling)
Both
Acute Myelogenous Leukemia, Myelodysplastic Syndrome

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Trial Information

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)


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.


Inclusion Criteria:



- 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.

Exclusion Criteria:

- 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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.

Outcome Description:

Primary outcome measure for the Phase 1 part of the study.

Outcome Time Frame:

Average 28 days after the first dose of treatment

Safety Issue:

Yes

Principal Investigator

Anthony S Stein, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

RT12-US-AML-a

NCT ID:

NCT01795924

Start Date:

January 2013

Completion Date:

March 2015

Related Keywords:

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

City of HopeDuarte, California  91010