Clinical Trials /

Phase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia

NCT03844997

Description:

The purpose of this study is to evaluate the safety and tolerability of Palbociclib in combination with investigational (experimental) drug, CPX-351 and evaluate the efficacy of Palbociclib in combination with chemotherapy as measured by overall response rate (ORR), i.e. complete response (CR) and CR with incomplete blood count recovery (CRi) by 2003 IWG criteria.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia
  • Official Title: Phase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: CASE1918
  • NCT ID: NCT03844997

Conditions

  • Acute Myeloid Leukemia
  • AML

Interventions

DrugSynonymsArms
PalcociclibIBRANCEPalbociclib + CPX-351
CPX-351VYXEOSPalbociclib + CPX-351

Purpose

The purpose of this study is to evaluate the safety and tolerability of Palbociclib in combination with investigational (experimental) drug, CPX-351 and evaluate the efficacy of Palbociclib in combination with chemotherapy as measured by overall response rate (ORR), i.e. complete response (CR) and CR with incomplete blood count recovery (CRi) by 2003 IWG criteria.

Detailed Description

      The objectives of this study are to evaluate the safety and tolerability of Palbociclibin
      combination with CPX-351, and to evaluate the efficacy of Palbociclibin combination with
      chemotherapy as measured by overall response rate (ORR), i.e. complete response (CR) and CR
      with incomplete blood count recovery (CRi) by IWG criteria.

      CPX-351 is an investigational drug that works as formulation of a fixed combination of the
      antineoplastic (acting to prevent, inhibit or halt the development of a neoplasm (a tumor))
      drugs cytarabine and daunorubicin.

      Palbociclibis an investigational drug that works to induce early G1 arrest by inhibiting
      CDK4/6, which are two types of CDKs that are overexpressed in AML cell cancer lines.

      CPX-351 and Palbociclib is experimental because it is not approved by the Food and Drug
      Administration (FDA).

      This is a single arm, open label study of the combination of Palbociclib with CPX-351 in
      adults with AML. The trial consists of two components: phase I to evaluate the safety with
      dose escalation of Palbociclib in combination with CPX-351 and phase II to evaluate the
      overall response rate of the combination in the targeted participant population.
    

Trial Arms

NameTypeDescriptionInterventions
Palbociclib + CPX-351ExperimentalPalbociclib will be administered orally on day -1 and -2 at 125 mg PO during the phase IIaportion (dose level 0).Day 0 will be rest and then CPX-351 at 100 u/m2 will be started on days 1, 3, and 5 along with Palbociclib day 2, 4, and 6 followed by rest/monitoring period (day 7-28). If Grade 3-4 non-hematologic toxicity is observed in 1 or less of 6 patients treated, the study will move to Phase IIb. If Grade 3-4 non-hematologic toxicity is observed in 2 or more of 6 patients treated, 6 additional patients will be treated on the Phase IIa portion at a lower dose level (100 mg po) until a Phase IIb safe dose schedule is defined at which 1 or less out of 6 patients on the Phase IIa experience Grade 3-4 non-hematologic toxicity. After the Phase IIa portion ensures safety, the study will proceed with phase IIb. The phase IIb component is a Simon 2-stage design trial whose objective is to assess the clinical efficacy of the combination of Palbociclib and CPX-351.
  • Palcociclib
  • CPX-351

Eligibility Criteria

        Inclusion Criteria:

          -  Newly diagnosed acute myeloid leukemia according to 2016 WHO criteria(excluding APL
             [AML-M3]).

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status <2

          -  Subjects must have normal organ function as defined below:

          -  Total bilirubin <2 times upper limit of normal ((≤ 3 x ULN if considered to be due to
             leukemic involvement or Gilbert's syndrome) or if higher than 2 times upper limit of
             normal with approval from the PI

          -  Serum Creatinine <2 x ULNor if higher than 2 times upper limit of normal with approval
             from the PI

          -  Left ventricular ejection fraction of ≥45%

          -  Patients with secondary AML arising out of MDS (all subtypes under WHO
             classification), chronic myelomonocytic leukemia (CMML) and therapy-related AML are
             eligible.

          -  Women of childbearing potential should be advised to avoid becoming pregnant and men
             should be advised to not father a child while receiving treatment. All men and women
             of childbearing potential must use acceptable methods of birth control throughout the
             study

          -  Subjects must have the ability to understand and the willingness to sign a written
             informed consent document.

        Exclusion Criteria:

          -  Prior treatment with CPX-351, Palbociclib or other cell cycle inhibitors.

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that, in
             the view of the treating physician, would place the participant at an unacceptable
             risk if he or she were to participate in the study or would prevent that person from
             giving informed consent.

          -  Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the
             past 6 months of starting the study drug (other than curatively treated
             carcinoma-in-situ of the cervix or non-melanoma skin cancer).

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to CPX-351, Palbociclib or other cell cycle inhibitors.

          -  Subjects with uncontrolled intercurrent illness including, but not limited to ongoing
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,
             uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  Known history of HIV or active hepatitis B or C.

          -  No major surgery within 2 weeks prior to study enrollment.

          -  Pregnancy or breast feeding

          -  Male and female patients who are fertile who do not agree to use an effective barrier
             methods of birth control (i.e. abstinence) to avoid pregnancy while receiving study
             treatment.

          -  Acute promyelocytic leukemia (APL)
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of experimental dose of Palbociclibin combination with CPX-351 as measured by number of participants with dose limiting toxicities.
Time Frame:Between days 28-35 of starting treatment
Safety Issue:
Description:If Grade 3-4 non-hematologic toxicity is observed in 1 or less of 6 patients treated, the dose of the study drug will be considered safe/tolerable. If Grade 3-4 non-hematologic toxicity is observed in 2 or more of 6 patients treated, 6 additional patients will be treated on the Phase IIa portion at a lower dose level (100 mg po).

Secondary Outcome Measures

Measure:Time to response (TTR)
Time Frame:Up to 2 years from end of treatment
Safety Issue:
Description:TTR measured between start of treatment and the date of achievement of response (responses defined per 2003 IWG criteria).
Measure:Duration of response (DOR)
Time Frame:Up to 2 years from end of treatment
Safety Issue:
Description:DOR is measured between the date of response to date of loss of response.
Measure:Event-free survival (EFS)
Time Frame:Up to 2 years from end of treatment
Safety Issue:
Description:EFS measured from the date of entry into a study to the date of primary refractory disease, or relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined
Measure:Overall Survival (OS) probability
Time Frame:Up to 2 years from end of treatment
Safety Issue:
Description:OS probability measured from the date of entry into a clinical trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aziz Nazha

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