Study of Palbociclib in MLL-rearranged Acute Leukemias

Sponsor

University of Ulm (Other)

Overall Status

Unknown status

CT.gov ID

NCT02310243

Collaborator

Pfizer (Industry), National Center for Tumor Diseases, Heidelberg (Other)

Enrollment

Locations

Arm

Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

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 :

Jul 1, 2015

Anticipated Primary Completion Date :

Jul 1, 2019

Anticipated Study Completion Date :

Jul 1, 2019

Arms and Interventions

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 Names: PD-0332991-00

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 Names:

PD-0332991-00

Outcome Measures

Primary Outcome Measures

Number of Participants with Adverse Events [12 months]
Safety assessments
Maximum tolerated dose of palbociclib [12 months]
overall response rate [12 months]

Secondary Outcome Measures

Relapse-free survival [three years]
Overall survival [three years]
Evaluation of target (CDK6) inhibition by palbociclib [three years]
Assessment of Quality of life [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Klinikum Augsburg	Augsburg	Germany	86156
2	Helios Klinikum Bad Saarow	Bad Saarow	Germany	15526
3	Charité Campus Benjamin Franklin	Berlin	Germany	12200
4	Vivantes Klinikum Neukölln	Berlin	Germany	12351
5	Charité Campus Virchow-Klinikum	Berlin	Germany	13353
6	Universitätsklinikum Bonn	Bonn	Germany	53105
7	Städtisches Klinikum Braunschweig gGmbH	Braunschweig	Germany	38114
8	Universitätsklinikum Düsseldorf	Düsseldorf	Germany	40225
9	Kliniken Essen Süd, Ev. Krankenhaus Essen-Werden gGmbH	Essen	Germany	45239
10	Malteser Krankenhaus St. Franziskus-Hospital	Flensburg	Germany	24939
11	Universitätsklinikum Freiburg	Freiburg	Germany	791016
12	MVZ Osthessen	Fulda	Germany	36043
13	Universitätsklinikum Giessen	Giessen	Germany	35392
14	Universitätsklinikum Hamburg-Eppendorf	Hamburg	Germany	20246
15	Medizinische Hochschule Hannover	Hannover	Germany	30625
16	Universitätsklinikum Heidelberg	Heidelberg	Germany	69120
17	Städtisches Klinikum Karlsruhe gGmbH	Karlsruhe	Germany	76133
18	Universitätsklinikum Schleswig-Holstein Campus Kiel	Kiel	Germany	24116
19	Caritas-Krankenhaus Lebach	Lebach	Germany	66822
20	Uni-Klinikum der Otto-von-Guericke-Universität	Magdeburg	Germany	39120
21	Universitätsmedizin der Johannes Gutenberg-Universität	Mainz	Germany	55131
22	Pius Hospital Oldenburg	Oldenburg	Germany	26121
23	Medizinische Universitätsklinik Tübingen	Tübingen	Germany	72076
24	University Hospital of Ulm	Ulm	Germany	89081