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

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ClinicalTrials.gov Identifier: NCT02438761
Recruitment Status : Active, not recruiting
First Posted : May 8, 2015
Last Update Posted : August 28, 2017
Sponsor:
Collaborators:
Fondation ARC
National Cancer Institute, France
Information provided by (Responsible Party):
Institut Curie

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.

Condition or disease Intervention/treatment Phase
Therapy-related Acute Myeloid Leukemia and Myelodysplastic Syndrome Acute Myeloid Leukemia, in Relapse de Novo Acute Myeloid Leukemia at Diagnostic Drug: PF-05212384 Phase 2

Detailed Description:

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.

Blood tests (hemogram) are assessed weekly before each injection of PF-05212384 (PKI-587). Bone marrow aspiration (myelogram) is performed to evaluate the response before starting treatment and before the start of cycle 3 (after two cycles) and at the end of the study (after four cycles). Good responders who continue treatment after four cycles will be evaluated by bone marrow aspiration (myelogram) every two cycles and after the end of treatment


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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.
Actual Study Start Date : August 31, 2015
Actual Primary Completion Date : May 10, 2017
Estimated Study Completion Date : May 2018


Arm Intervention/treatment
Experimental: PF-05212384
150 mg Intra-venous every week
Drug: PF-05212384

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.

Other Name: PKI-587




Primary Outcome Measures :
  1. To evaluate the efficacy of PF-05212384 [ Time Frame: 4 months after treatment ]
    The overall response rate will be assessed according to the International Working Group (IWG) AML and MDS criteria (by B.D. Cheson).


Secondary Outcome Measures :
  1. Tolerance and toxicity during treatment [ Time Frame: 4 months ]
    Issued the Common Terminology Criteria for Adverse Events (CTCAE) version 4 National Cancer Institute (NCI)

  2. Treatment compliance [ Time Frame: 4 months ]
    Treatment compliance will be assessed by the ratio between the number of cycles administered on the expected number of cycles, and on time between treatment cycles

  3. Progressive Free Survival (PFS) [ Time Frame: one year ]
    Progressive Free Survival at one year from the date of inclusion to the date of progression of the disease or death

  4. Overall survival [ Time Frame: 48 months ]
    Overall Survival from the date of inclusion to the date of death

  5. Evaluation of Quality of life [ Time Frame: 4 months ]
    Quality of life (QLQ-C30) questionnaire according to European Organisation for Research and Treatment of Cancer (EORTC)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02438761


Locations
France
Hôpital Saint-Louis
Paris, Ile de France, France, 75475
Hôpital Cochin
Paris, Ile de France, France, 75679
Institut Curie - Hôpital René Huguenin
Saint-Cloud, Ile de France, France, 92210
CHU de Toulouse
Toulouse, Midi-Pyrénées, France, 31059
Institut Paoli Calmette
Marseille, Paca, France, 13009
Sponsors and Collaborators
Institut Curie
Fondation ARC
National Cancer Institute, France
Investigators
Principal Investigator: Jacques Vargaftig, MD Institut Curie - Hôpital René Huguenin

Responsible Party: Institut Curie
ClinicalTrials.gov Identifier: NCT02438761     History of Changes
Other Study ID Numbers: IC 2014-10 LAM-PIK
First Posted: May 8, 2015    Key Record Dates
Last Update Posted: August 28, 2017
Last Verified: February 2017

Keywords provided by Institut Curie:
Acute Myeloid Leukemia
Myelodysplastic Syndrome
PIK/Akt/mTor

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions