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

NCT02438761 | Terminated Phase 2

• 1 other identifier: IC 2014-10
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 5

Brief Summary

Phase II open-label single-arm prospective multicentric clinical trial of PF-05212384 (PKI-587) delivered by intravenous route. A 2-stage Fleming design will be employed.

Conditions

Therapy-related Acute Myeloid Leukemia and Myelodysplastic Syndrome; Acute Myeloid Leukemia, in Relapse; de Novo Acute Myeloid Leukemia at Diagnostic

Keywords

Acute Myeloid Leukemia; Myelodysplastic Syndrome; PIK/Akt/mTor

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy of PF-05212384

  The overall response rate will be assessed according to the International Working Group (IWG) AML and MDS criteria (by B.D. Cheson).

  4 months after treatment

Secondary Outcomes (5)

• Tolerance and toxicity during treatment

  4 months

• Treatment compliance

  4 months

• Progressive Free Survival (PFS)

  one year

• Overall survival

  48 months

• Evaluation of Quality of life

  4 months

Study Arms (1)

PF-05212384

EXPERIMENTAL

150 mg Intra-venous every week

Drug: PF-05212384

Interventions

PF-05212384 DRUG

PF-05212384 will be delivered by intra-venous route at a fixed dose of 150 mg per week. Each treatment cycle includes four weekly injections The treatment is administered in cycles of 28 days for a period of 4 cycles. Patients will be treated on a weekly basis continuously during 112 days or until progression.

Also known as: PKI-587

PF-05212384

Eligibility Criteria

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

You may qualify if:

• 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)
• Adequate glycemic balance defined by glycated hemoglobin ≤ 8%
• Females of childbearing potential (FCBP) should receive effective contraception: a negative pregnancy blood test is required within 2 weeks before starting experimental treatment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
• Absence of severe or active infection
• Adequate systolic cardiac function : Left Ventricular Ejection Fraction (LVEF) ≥ 50%
• 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
• Adequate renal function: serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance \> 60 ml/min.
• Signed informed consent

You may not qualify if:

• Glucose intolerance or diabetes mellitus, treated or untreated
• 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
• AML secondary to MDS or myeloproliferative syndrome (WHO 2008 definitions)
• Acute Promyelocytic Leukaemia (APL or AML French American British (FAB) classification 3) de novo or secondary to treatment (t-APL)
• de novo or secondary Core Binding Factor (CBF)/AML
• 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
• Leukocytes above 30.000/mm3 (30 G/L) at enrollment
• Antileukemic treatment within 15 days before enrollment, with the exception of hydroxyurea
• Central nervous system leukemic involvement
• Pregnant or lactating women, or women of childbearing potential without effective contraception
• Prior history of allogeneic bone marrow transplantation
• Prior history of organ transplantation or other cause of severe or chronic immunodeficiency Human
• Seropositivity for Human Immunodeficiency Virus (HIV) or Human T-Lymphotropic Virus-1 (HTLV-1) viruses, active B or C hepatitis
• Patients unable to undergo medical monitoring for geographical, social or psychological issues
• Patient under measure of legal protection

Sponsors & Collaborators

• Institut Curie: lead
• Fondation ARC: collaborator
• National Cancer Institute, France: collaborator

Study Sites (5)

CHU de Toulouse

Toulouse, Midi-Pyrénées, 31059, France

Location

Institut Paoli Calmette

Marseille, PACA, 13009, France

Location

Hôpital Saint-Louis

Paris, Île-de-France Region, 75475, France

Location

Hôpital Cochin

Paris, Île-de-France Region, 75679, France

Location

Institut Curie - Hôpital René Huguenin

Saint-Cloud, Île-de-France Region, 92210, France

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

gedatolisib

Condition Hierarchy (Ancestors)

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

Study Officials

• Jacques Vargaftig, MD

  Institut Curie - Hôpital René Huguenin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2015
• First Posted: May 8, 2015
• Study Start: August 31, 2015
• Primary Completion: May 10, 2017
• Study Completion: April 23, 2018
• Last Updated: September 8, 2025

Record last verified: 2019-02

Locations

FR (5)