Clinical Trials /

Study of Palbociclib in MLL-rearranged Acute Leukemias

NCT02310243

Description:

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.

Related Conditions:
  • Acute Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Palbociclib in MLL-rearranged Acute Leukemias
  • Official Title: Phase Ib/IIa Study of Palbociclib in MLL-rearranged Acute Leukemias AMLSG 23-14/Palbo-AL-1

Clinical Trial IDs

  • ORG STUDY ID: AMLSG 23-14
  • NCT ID: NCT02310243

Conditions

  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
PalbociclibPD-0332991-00Palbociclib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
PalbociclibExperimentalPhase1b: 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.
  • Palbociclib

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Adverse Events
Time Frame:12 months
Safety Issue:
Description:Safety assessments

Secondary Outcome Measures

Measure:Relapse-free survival
Time Frame:three years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:three years
Safety Issue:
Description:
Measure:Evaluation of target (CDK6) inhibition by palbociclib
Time Frame:three years
Safety Issue:
Description:
Measure:Assessment of Quality of life
Time Frame:6 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Ulm

Trial Keywords

  • Acute myeloid leukemia
  • Acute lymphoblastic leukemia
  • MLL-rearranged leukemia
  • Palbociclib (PD-0332991-00)

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