Phase II clinical trial evaluating the efficacy of PF-05212384 (PKI-587) for patients with myeloid neoplasm secondary to chemo-radiotherapy (t-AML/MDS) or de novo relapsed or refractory AM

Phase 1

• Conditions: Myeloid neoplasm secondary to chemo-radiotherapy (t-AML/MDS) /or relapsed or refractory de novo AML /or de novo AML at diagnostic considered unfit to benefit from induction therapy with chemotherapy associated aplasia; MedDRA version: 17.1Level: LLTClassification code 10066572Term: AML progressionSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-002752-50-FR
• Lead Sponsor: INSTITUT CURIE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-07
• Last Update Posted: 22 May 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Patients belong to one of three categories:
1.1. Myeloid neoplasm secondary to chemo-radiotherapy (t-AML/MDS) aged 60 and over with unfavorable cytogenetics (ELN 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
1.2. 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
1.3. 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 (HbA1c) = 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. ECOG/performance status = 2
5. Absence of severe or active infection
6. Adequate systolic cardiac function (LVEF = 50%)
7. Adequate hepatic function: AST and 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 39
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 39

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 FAB3) de novo or secondary to treatment (t-APL)
5. de novo or secondary CBF/AML
6. de novo or secondary Ph1 positive AML defined by the presence of a t(9.22) or a 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
13. Seropositivity for HIV or 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of PF-05212384 (PKI-587) on the overall response after treatment;Secondary Objective: -Tolérance and toxicity <br>-Treament compliance <br>-PFS and Overall survival <br>-Quality of life<br>;Primary end point(s): The overall response rate will be assessed according to the IWG AML and MDS criteria (by Cheson BD). The primary endpoint will be the rates of CR + CRu + PR evaluated.;Timepoint(s) of evaluation of this end point: 4 months after inclusion

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Tolerance and toxicity NCI CTCAE V4 scoring system<br>-Treatment compliance will be evaluated by the ratio between the number of cycles administered on the expected number of cycles and deadlines between treatment cycles.<br>-Progression Free Survival will be calculated from the date of inclusion until progression or death and the Overall survival will also be calculated from the date of inclusion to de date of death. <br>-Quality of life using QLQ-C30 EORTC<br><br>;Timepoint(s) of evaluation of this end point: -Tolerance and toxicity during treatment<br>-Treatment compliance during treatment<br>-Duration of response PFS at one year <br>-Overall survival (date of death) <br>-Quality of Iife at the end of induction and maintenance therapy<br>