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JOURNAL ONKOLOGIE – STUDIE

First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia

Rekrutierend

NCT-Nummer:
NCT04067336

Studienbeginn:
September 2019

Letztes Update:
15.03.2024

Wirkstoff:
Ziftomenib

Indikation (Clinical Trials):
Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute, Leukemia, Biphenotypic, Acute, Acute Disease

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Kura Oncology, Inc.

Collaborator:
-

Kontakt

Studienlocations
(3 von 52)

Charitè-Campus Benjamin Franklin
12203 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
University Medicine Greifswald
17475 Greifswald
(Mecklenburg-Vorpommern)
GermanyRekrutierend» Google-Maps
Medizinische Hochsschule Hannover
Hannover
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Johannes Gutenberg - University Mainz
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
46202 Indianapolis
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Jill Weisenbach, RN
Phone: 317-278-0597
E-Mail: Jweisenb@iupui.edu» Ansprechpartner anzeigen
University of Maryland Greenebaum Comprehensive Cancer Center
21201 Baltimore
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Larissa Sanglard, MD
Phone: 410-328-8370
E-Mail: larissa.sanglard@umm.edu» Ansprechpartner anzeigen
Hackensack University Medical Center - John Theurer Cancer Center
07601 Hackensack
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Lumi Demirovic
Phone: 551-996-8154
E-Mail: Ljumnije.demirovic@hmhn.org» Ansprechpartner anzeigen
Weill Cornell Medical College - NY Presbyterian Hospital
10021 New York
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Tania Curcio
Phone: 212-746-2571
E-Mail: tjc9003@med.cornell.edu» Ansprechpartner anzeigen
Harold C. Simmons Comprehensive Cancer Center - UT Southwestern Medical Center
75390 Dallas
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Yasmeen Akhtar, MBBS,MS,CCRP
Phone: 214-648-5130
E-Mail: Yasmeen.Akhtar@UTSouthwestern.edu» Ansprechpartner anzeigen
Fred Hutchinson Cancer Research Center
98109 Seattle
United StatesAktiv, nicht rekrutierend» Google-Maps
Queen Elizabeth II Health Sciences Centre
B3H 1V7 Halifax
CanadaRekrutierend» Google-Maps
Hopital Maisonneuve-Rosemont
H1T 2M4 Montréal
CanadaRekrutierend» Google-Maps
Hopital de l'Enfant-Jesus - Centre Integre en Cancerologie du CHU de Quebec - Universite Laval
G1J 1Z4 Québec
CanadaRekrutierend» Google-Maps
CHU de Quebec - Universite Laval, Hopital de l'Enfant - Jesus
G1S 4L8 Québec
CanadaRekrutierend» Google-Maps
Centre Hospitalier Lyon Sud
69310 Pierre-Bénite
FranceRekrutierend» Google-Maps
Institute of Hematology and Medical Oncology "L. and A. Seragnoli"
40138 Bologna
ItalyRekrutierend» Google-Maps
IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"
47014 Meldola
ItalyRekrutierend» Google-Maps
UO Ematologia Ospedale di Ravenna
48121 Ravenna
ItalyRekrutierend» Google-Maps
Institution Fondazione Policlinico Tor Vergata
Roma
ItalyRekrutierend» Google-Maps
Hospital Universitari Vall d'Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps
Hospital Universitario HM Sanchinarro
28050 Madrid
SpainRekrutierend» Google-Maps
Hospital Universitario Central de Asturias
33011 Oviedo
SpainRekrutierend» Google-Maps
Hospital Universitario Virgen del Rocio
41013 Sevilla
SpainRekrutierend» Google-Maps
Hospital Universitari i Politecnic La Fe
46026 Valencia
SpainRekrutierend» Google-Maps
Beatson West of Scotland Cancer Centre
G12 0YN Glasgow
United KingdomRekrutierend» Google-Maps
St. George's Hospital
SW17 0QT London
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This Phase 1/2, first-in-human (FIH), open-label, dose-escalation and

dose-validation/expansion study will assess ziftomenib, a menin-MLL(KMT2A) inhibitor, in

patients with relapsed or refractory acute myeloid leukemia (AML).

The dose-escalation part of the study (Phase 1a) will determine the maximal tolerated dose

(MTD) and/or the recommended Phase 2 dose (RP2D).

The dose-validation/expansion part of the study (Phase 1b) will determine the safety,

tolerability, and minimal biologically effective dose of ziftomenib in dosing cohorts which

have demonstrated early biological activity and have been determined to be safe in the

dose-escalation phase.

The Phase 2 portion of the study will determine the safety, tolerability, and anti-leukemia

activity of ziftomenib in patients with NPM1-m AML.

Ein-/Ausschlusskriterien

Key Inclusion Criteria:

Patients with refractory or relapsed AML defined as the reappearance of ≥ 5% blasts in the

bone marrow and who have also failed or are ineligible for any approved standard of care

therapies, including HSCT.

1. Phase 1b:

1. Patients with a documented lysine[K]-specific methyltransferase 2-rearrangement

(KMT2A-r), or

2. Patients with a documented nucleophosmin 1 mutation (NPM1-m)

2. Phase 2:

a. Patients with a documented nucleophosmin 1 mutation (NPM1-m)

3. ≥ 18 years of age.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life

expectancy of at least 2 months.

5. Adequate liver and kidney function according to protocol requirements.

6. Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea

to control and maintain white blood cell count prior to enrollment.

7. Women of childbearing potential must be willing to use a highly effective method of

contraception throughout the study and for at least 180 days after the last dose of

study treatment.

8. Males with female partners of childbearing potential must agree to use a highly

effective method of contraception throughout the study and for at least 90 days after

the last dose of study treatment.

Key Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia.

2. Diagnosis of chronic myelogenous leukemia in blast crisis.

3. Donor lymphocyte infusion < 30 days prior to study entry.

4. Clinically active central nervous system (CNS) leukemia.

5. Undergone HSCT and have not had adequate hematologic recovery.

6. Receiving immunosuppressive therapy post HSCT within 2 weeks of Cycle 1 Day 1.

7. Grade ≥ 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic

GVHD, or extensive chronic GVHD of any severity.

8. Received chemotherapy immunotherapy, radiotherapy, or any ancillary therapy that is

considered to be investigational (i.e., used for non-approved indications(s) and in

the context of a research investigation) < 14 days prior to the first dose of

ziftomenib or within 5 drug half-lives prior to the first dose of study drug.

9. Not recovered to < Grade 2 (National Cancer Institute Common Terminology Criteria for

Adverse Events v5.0) from all acute toxicities or deemed back to a stable baseline.

10. Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome

P450-isozyme 3A4 (CYP3A4) with the exception of antibiotics, antifungals, and

antivirals that are used as standard of care or to prevent or treat infections and

other such drugs that are considered absolutely essential for the care of the patient.

11. Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B

surface antigen indicative of active infection. Patients with controlled disease will

not be excluded from study enrollment.

12. Pre-existing disorder predisposing the patient to a serious or life-threatening

infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding

disorder, or cytopenias not related to AML).

13. Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other

infection.

14. Significant cardiovascular disease including unstable angina pectoris, uncontrolled

hypertension or arrhythmia, history of cerebrovascular accident including transient

ischemic attack within the past 6 months, congestive heart failure (NYHA Class III or

IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or

a myocardial infarction within 6 months prior to the first dose of study treatment.

15. Mean QTcF >480 ms on triplicate ECG.

16. Major surgery within 4 weeks prior to the first dose of study treatment.

17. Women who are pregnant or lactating. All female patients with reproductive potential

must have a negative serum pregnancy test within 72 hours prior to starting treatment.

Studien-Rationale

Primary outcome:

1. Phase 1a: Maximal tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) (Time Frame - Dose Limiting Toxicities (DLTs) will be evaluated during the first 28 days (1 cycle)):
MTD is defined as the highest dose that is not expected to cause dose limiting toxicity (DLT) in more than 20% of patients.

2. Phase 1b: Number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs). (Time Frame - During treatment and up to approximately 28 days after treatment discontinuation, or until immediately before the initiation of another anticancer therapy, whichever occurs first.):
Assessed by NCI-CTCAE v5.0

3. Phase 1b: Minimal biologically effective dose (Time Frame - Up to 12 months following end of treatment):
Minimal biologically effective dose in dosing cohorts which have demonstrated biological activity and have been determined to be safe as a part of Part 1a

4. Phase 2: Evidence of anti-leukemia activity (Time Frame - 12 months following end of treatment):
Anti-leukemia activity is assessed by the CR (CR+CRh) rate

Secondary outcome:

1. Phase 1a: Number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs). (Time Frame - During treatment and up to approximately 28 days after treatment discontinuation, or until immediately before the initiation of another anticancer therapy, whichever occurs first.):
Assessed by NCI-CTCAE v5.0

2. Phase 1a: Tmax (Time Frame - Cycle 1 and Cycle 2. Each cycle is 28 days.):
Time to observed maximum plasma concentration of ziftomenib and/or its metabolites

3. Phase 1a: AUC(0-last) (Time Frame - Cycle 1 and Cycle 2. Each cycle is 28 days.):
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration of ziftomenib and/or its metabolites

4. Phase 1a: Cmax (Time Frame - Cycle 1 and Cycle 2. Each cycle is 28 days.):
Maximum plasma concentration of ziftomenib and/or its metabolites

5. Phases 1a, 1b, and 2: Composite definition of complete remission (CR) and complete remission with partial hematologic recovery (CRh) (Time Frame - Up to 12 months following discontinuation of treatment):
To assess the CR (CR+CRh) rate

6. Phases 1a, 1b, and 2: Complete response (CR) with and without minimal residual disease (MRD) (Time Frame - Up to 12 months following discontinuation of treatment):
To assess the CR rate with and without MRD

7. Phases 1a, 1b, and 2: Duration of remission (DOR) (Time Frame - Up to 12 months following discontinuation of treatment):
To assess the DOR

8. Phases 1a, 1b, and 2: Transfusion independence (TI) (Time Frame - Up to 12 months following discontinuation of treatment):
To assess transfusion independence

9. Phases 1a, 1b, and 2: Event-free survival (EFS) (Time Frame - Up to 12 months following discontinuation of treatment):
To assess event-free survival

10. Phases 1a, 1b, and 2: Overall survival (Time Frame - Up to 12 months following discontinuation of treatment):
To assess overall survival

Studien-Arme

  • Experimental: Phase 1a - Dose Escalation
  • Experimental: Phase 1b - Dose-Validation Expansion
    Cohort 1: KMT2A-r / NPM1-m patients will receive a dose previously studied in Phase 1a Cohort 2: KMT2A-r / NPM1-m patients will receive a dose previously studied in Phase 1a
  • Experimental: Phase 2
    NPM1-m patients will receive the recommended phase 2 dose determined in Phase 1

Geprüfte Regime

  • Ziftomenib:
    Oral administration

Quelle: ClinicalTrials.gov


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