PF-05212384 (PKI-587) for t-AML/MDS or de Novo Relapsed or Refractory Acute Myeloid Leukemia (AML)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02438761
• Date of registration: 06/05/2015
• Prospective Registration: Yes
• Primary sponsor: Institut Curie
• Public title: PF-05212384 (PKI-587) for t-AML/MDS or de Novo Relapsed or Refractory Acute Myeloid Leukemia (AML) LAM-PIK
• Scientific title: Phase II Evaluating the Efficacy of the Dual Inhibition of Phosphoinositide 3 Kinase (PI3K)/Akt /Mammalian Target Of Rapamycine (mTOR) Signaling Pathway by PF-05212384 (PKI-587) for Patients With Myeloid Neoplasm Secondary to Chemo-radiotherapy (t-AML/MDS) or de Novo Relapsed or Refractory AML.
• Date of first enrolment: August 31, 2015
• Target sample size: 10
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02438761
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Jacques Vargaftig, MD
• Affiliation: Institut Curie - Hôpital René Huguenin

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patients belong to one of three categories:

- Myeloid neoplasm secondary to chemo-radiotherapy (t-AML/MDS) aged 60 and over
with unfavorable cytogenetics (European Leukemia Network definition 2010), the
first cancer must have been in remission for more than two years, except in situ
carcinoma, basal cell carcinoma and squamous cell carcinoma

- Relapsed or refractory de novo AML aged 18 and over (multiple relapses allowed),
regardless of the risk group, provided not being eligible for allogeneic bone
marrow transplantation

- de novo AML at diagnosis, aged 60 and over and considered unfit to benefit from
induction chemotherapy associated with aplasia (at the discretion of the
investigator)

2. Adequate glycemic balance defined by glycated hemoglobin = 8%

3. Females of childbearing potential (FCBP) should receive effective contraception: a
negative pregnancy blood test is required within 2 weeks before starting experimental
treatment.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 2

5. Absence of severe or active infection

6. Adequate systolic cardiac function : Left Ventricular Ejection Fraction (LVEF) = 50%

7. Adequate hepatic function: Aspartate Aminotransferase Test (AST) and Alanine
Aminotransferase Test (ALT) = 3 times the upper limit of normal (ULN), bilirubin = 1.5
x ULN

8. Adequate renal function: serum creatinine = 1.5 x ULN or calculated creatinine
clearance > 60 ml/min.

9. Signed informed consent

Exclusion Criteria:

1. Glucose intolerance or diabetes mellitus, treated or untreated

2. First cancer in evolution(solid tumor or lymphoma) or in remission for less than two
years, except in situ carcinoma, basal cell carcinoma and squamous cell carcinoma

3. AML secondary to MDS or myeloproliferative syndrome (WHO 2008 definitions)

4. Acute Promyelocytic Leukaemia (APL or AML French American British (FAB) classification
3) de novo or secondary to treatment (t-APL)

5. de novo or secondary Core Binding Factor (CBF)/AML

6. de novo or secondary Philadelphia Chromosome (Ph) 1 positive AML defined by the
presence of a t(9.22) or a Breakpoint Cluster Region-Abelson Murine Leukemia Viral
Oncogene Homolog (BCR-ABL) transcript

7. Leukocytes above 30.000/mm3 (30 G/L) at enrollment

8. Antileukemic treatment within 15 days before enrollment, with the exception of
hydroxyurea

9. Central nervous system leukemic involvement

10. Pregnant or lactating women, or women of childbearing potential without effective
contraception

11. Prior history of allogeneic bone marrow transplantation

12. Prior history of organ transplantation or other cause of severe or chronic
immunodeficiency Human

13. Seropositivity for Human Immunodeficiency Virus (HIV) or Human T-Lymphotropic Virus-1
(HTLV-1) viruses, active B or C hepatitis

14. Inclusion in another experimental anti-cancer clinical trial*

15. Patients unable to undergo medical monitoring for geographical, social or
psychological issues

16. Patient under measure of legal protection

17. No social security

- For ethical reasons, the exclusion period before considering the possibility of
participating in another clinical study with a new experimental molecule cannot
be determined, yet each case will be discussed on an individual basis with the
study coordinator.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Acute Myeloid Leukemia, in Relapse

de Novo Acute Myeloid Leukemia at Diagnostic

Therapy-related Acute Myeloid Leukemia and Myelodysplastic Syndrome

Intervention(s)

Drug: PF-05212384

Primary Outcome(s)

To evaluate the efficacy of PF-05212384 [Time Frame: 4 months after treatment]

Secondary Outcome(s)

Tolerance and toxicity during treatment [Time Frame: 4 months]

Progressive Free Survival (PFS) [Time Frame: one year]

Evaluation of Quality of life [Time Frame: 4 months]

Overall survival [Time Frame: 48 months]

Treatment compliance [Time Frame: 4 months]

Secondary ID(s)

IC 2014-10 LAM-PIK

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Fondation ARC

National Cancer Institute, France