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Study of Palbociclib in MLL-rearranged Acute Leukemias

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ClinicalTrials.gov Identifier: NCT02310243
Recruitment Status : Recruiting
First Posted : December 8, 2014
Last Update Posted : May 19, 2017
Sponsor:
Collaborators:
Pfizer
Nationales Centrum für Tumorerkrankungen Heidelberg
Information provided by (Responsible Party):
Peter Paschka, University of Ulm

Brief Summary:

Diagnosis: Acute myeloid leukemia; Acute lymphoblastic leukemia Age ≥ 18 years, no upper age limit Study drug: Palbociclib Phase Ib/IIa, open-label

  • Phase Ib: Based on previous experience with 125 mg palbociclib once daily for 21 days followed by 7 days of rest in patients with breast cancer, liposarcoma, non-small cell lung cancer, hepatocellular carcinoma, ovarian cancer, mantle-cell lymphoma, and glioblastoma, this regimen will be chosen for the first dose to be evaluated in the phase Ib. Based on a 3 + 3 modified Fibonacci design, the tolerable dose of palbociclib for the phase IIa is defined.
  • Phase IIa: single-agent palbociclib using the tolerable dose defined in the phase Ib part of the study is administered once daily for 21 days followed by 7 days of rest. Based on the optimal two-stage design of Simon, 21 patients are treated in the first stage. If results are positive, 29 additional patients will be recruited into the second stage of the study. An efficacy of the investigational therapy will be rejected in the first stage of 21 treated patients if two or less patients achieve complete remission (CR), CR with incomplete blood count recovery (CRi), partial remission (PR), or anti-leukemic effect (ALE). If three or more patients achieve CR, CRi, PR, or ALE during this first stage, the trial is intended to be continued in the second stage with a total sample size of 50 patients.

Start of recruitment: July 2015 End of recruitment: July 2017 End of study (last patient out): July 2018 The treatment duration of an individual patient is estimated to be 2-6 months, but may be unlimited in patients with sustained response ("case-by-case decision").

Observation time per patient after entry into the study (incl. treatment) is at least 12 months.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Drug: Palbociclib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib/IIa Study of Palbociclib in MLL-rearranged Acute Leukemias AMLSG 23-14/Palbo-AL-1
Study Start Date : July 2015
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018


Arm Intervention/treatment
Experimental: Palbociclib

Phase1b: 125 mg palbociclib once daily for 21 days followed by 7 days of rest; this regimen will be chosen for the first dose to be evaluated.

phase IIa: single-agent palbociclib using the tolerable dose defined in the phase Ib part of the study is administered once daily for 21 days followed by 7 days of rest.

Drug: Palbociclib
oral, once daily (125mg, 100mg or 75mg) for 21 days
Other Name: PD-0332991-00




Primary Outcome Measures :
  1. Number of Participants with Adverse Events [ Time Frame: 12 months ]
    Safety assessments

  2. Maximum tolerated dose of palbociclib [ Time Frame: 12 months ]
  3. overall response rate [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Relapse-free survival [ Time Frame: three years ]
  2. Overall survival [ Time Frame: three years ]
  3. Evaluation of target (CDK6) inhibition by palbociclib [ Time Frame: three years ]
  4. Assessment of Quality of life [ Time Frame: 6 months ]


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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:

  • Patients with confirmed diagnosis of acute leukemia with MLL rearrangement according to the 2008 WHO Classification
  • Patients with MLL-rearranged leukemia who are refractory to standard induction therapy and not immediate candidates for allogeneic HSCT (bridge to transplant is allowed)
  • Patients with MLL-rearranged leukemia who relapsed after standard first-line treatment and are not immediate candidates for allogeneic HSCT (bridge to transplant is allowed)
  • Patients with newly diagnosed MLL-rearranged leukemia who are not eligible for intensive first-line therapy
  • Genetic/histologic/immunohistologic assessment in one of the central laboratories
  • Age ≥ 18 years, no upper age limit
  • WHO performance status of ≤ 2
  • No prior chemotherapy two weeks before study entry except hydroxyurea to control hyperleukocytosis
  • Non-pregnant and non-nursing. Women of child-bearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 72 hours prior to registration (WOCBP is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 months).
  • Female patients in the reproductive age and male patients must agree to avoid getting pregnant or to father a child while on therapy and for three months after the last dose of therapy.
  • Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin one acceptable method of birth control (IUD, tubal ligation, or partner's vasectomy). Hormonal contraception is an inadequate method of birth control.
  • Men must agree not to father a child and must use a latex condom during any sexual contact with WOCBP while receiving therapy and for three months after therapy is stopped, even if they have undergone successful vasectomy.
  • Signed written informed consent

Exclusion Criteria:

  • Prior treatment with palbociclib
  • Performance status > 2 according to WHO criteria
  • Organ insufficiency: creatinine > 1.5 x upper normal serum level; bilirubin, AST, or AP > 2.5 x upper normal serum level; heart failure NYHA III/IV; uncontrolled hypertension; unstable angina; serious cardiac arrhythmia; severe obstructive or restrictive ventilation disorder
  • Uncontrolled infection
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year.
  • Severe neurologic or psychiatric disorder interfering with ability of giving informed consent
  • Known or suspected active alcohol or drug abuse
  • Known positivity for HIV, active HAV, HBV, or HCV infection
  • Bleeding disorder unrelated to leukemia
  • Uncontrolled CNS involvement (treatment for CNS-involvement prior to inclusion is allowed)
  • QTc > 470 msec (based on the mean value of triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome, or known history of QTc prolongation or Torsade de Pointes
  • Uncontrolled electrolyte disorders that can aggravate the effects of a QTc-prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia)
  • No consent for registration, storage, and processing of individual disease characteristics, information on the course of the disease, and information obtained from the family physician and/or other physicians involved in the treatment of the patient about study participation
  • No consent for biobanking

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): NCT02310243


Locations
Germany
Klinikum Augsburg Recruiting
Augsburg, Germany, 86156
Contact: Christoph Schmid, MD       christoph.schmid@klinikum-augsburg.de   
Helios Klinikum Bad Saarow Recruiting
Bad Saarow, Germany, 15526
Contact: Daniel Schöndube, MD       daniel.schoendube@helios-kliniken.de   
Charité Campus Benjamin Franklin Recruiting
Berlin, Germany, 12200
Contact: Claudia Bladus, MD       claudia.baldus@charite.de   
Vivantes Klinikum Neukölln Recruiting
Berlin, Germany, 12351
Contact: Maike de Wit, MD       maike.dewit@vivantes.de   
Charité Campus Virchow-Klinikum Recruiting
Berlin, Germany, 13353
Contact: Jörg Westermann, MD       joerg.westermann@charite.de   
Universitätsklinikum Bonn Recruiting
Bonn, Germany, 53105
Contact: Karin Tina Mayer, MD       karin.mayer@ukb.uni-bonn.de   
Städtisches Klinikum Braunschweig gGmbH Recruiting
Braunschweig, Germany, 38114
Contact: Jürgen Krauter, MD       krauter.juergen@mh-hannover.de   
Universitätsklinikum Düsseldorf Recruiting
Düsseldorf, Germany, 40225
Contact: Thomas Schroeder, MD       thomas.schroeder@med.uni-duesseldorf.de   
Kliniken Essen Süd, Ev. Krankenhaus Essen-Werden gGmbH Recruiting
Essen, Germany, 45239
Contact: Mohammed Wattad, MD       m.wattad@kliniken-essen-sued.de   
Malteser Krankenhaus St. Franziskus-Hospital Recruiting
Flensburg, Germany, 24939
Contact: Nadezda Basara, MD       nadezda.basara@malteser.org   
Universitätsklinikum Freiburg Recruiting
Freiburg, Germany, 791016
Contact: Ralph Wäsch, MD       ralph.waesch@uniklinik-freiburg.de   
MVZ Osthessen Recruiting
Fulda, Germany, 36043
Contact: Andrea Distelrath, MD       distelrath@mvz-osthessen.de   
Universitätsklinikum Giessen Recruiting
Giessen, Germany, 35392
Contact: Maisun Abu Samara, MD       maisun.abu.samra@innere.med.uni-giessen.de   
Universitätsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Contact: Walter Fiedler, MD       fiedler@uke.de   
Medizinische Hochschule Hannover Recruiting
Hannover, Germany, 30625
Contact: Michael Heuser, MD       heuser.michael@mh-hannover.de   
Universitätsklinikum Heidelberg Recruiting
Heidelberg, Germany, 69120
Contact: Alwin Krämer, MD       Alwin.Kraemer@med.uni-heidelberg.de   
Städtisches Klinikum Karlsruhe gGmbH Recruiting
Karlsruhe, Germany, 76133
Contact: Mark Ringhoffer, MD       mark.ringhoffer@klinikum-karlsruhe.com   
Universitätsklinikum Schleswig-Holstein Campus Kiel Recruiting
Kiel, Germany, 24116
Contact: Heinz-August Horst, MD       h.horst@med2.uni-kiel.de   
Caritas-Krankenhaus Lebach Recruiting
Lebach, Germany, 66822
Contact: Stephan Kremers, MD       stephankremers@onkologie-lebach.de   
Uni-Klinikum der Otto-von-Guericke-Universität Recruiting
Magdeburg, Germany, 39120
Contact: Denise Wolleschak, MD       denise.wolleschak@med.ovgu.de   
Universitätsmedizin der Johannes Gutenberg-Universität Recruiting
Mainz, Germany, 55131
Contact: Thomas Kindler, MD       thomas.kindler@unimedizin-mainz.de   
Pius Hospital Oldenburg Recruiting
Oldenburg, Germany, 26121
Contact: Frank Griesinger, MD       frank.griesinger@pius-hospital.de   
Medizinische Universitätsklinik Tübingen Recruiting
Tübingen, Germany, 72076
Contact: Helmut Salih, MD       Helmut.Salih@med.uni-tuebingen.de   
University Hospital of Ulm Recruiting
Ulm, Germany, 89081
Contact: Peter Paschka, MD    0049-731-500 ext 45521    peter.paschka@uniklinik-ulm.de   
Sponsors and Collaborators
University of Ulm
Pfizer
Nationales Centrum für Tumorerkrankungen Heidelberg

Responsible Party: Peter Paschka, PD. Dr. med., University of Ulm
ClinicalTrials.gov Identifier: NCT02310243     History of Changes
Other Study ID Numbers: AMLSG 23-14
First Posted: December 8, 2014    Key Record Dates
Last Update Posted: May 19, 2017
Last Verified: May 2017

Keywords provided by Peter Paschka, University of Ulm:
Acute myeloid leukemia
Acute lymphoblastic leukemia
MLL-rearranged leukemia
Palbociclib (PD-0332991-00)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Palbociclib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action