Clinical Trials /

Palbociclib and Dexamethasone in Treating Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

NCT03472573

Description:

This phase I trial studies the side effects and best dose of palbociclib when given together with dexamethasone in treating participants with B-cell acute lymphoblastic leukemia that has come back after a period of improvement or does not respond to treatment. Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone is a steroid medication that is used in combination with other medications to treat B-cell acute lymphoblastic leukemia. Giving palbociclib together with dexamethasone may work better in treating patients with B-cell acute lymphoblastic leukemia.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Palbociclib and Dexamethasone in Treating Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
  • Official Title: A Phase I Trial of Palbociclib in Combination With Dexamethasone in Relapsed or Refractory Adult B-Cell Acute Lymphoblastic Leukemia (ALL)

Clinical Trial IDs

  • ORG STUDY ID: 17P.676
  • NCT ID: NCT03472573

Conditions

  • Recurrent B Acute Lymphoblastic Leukemia
  • Refractory B Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
Palbociclib571190-30-2, 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD-0332991Treatment (palbociclib, dexamethasone)
DexamethasoneBaycuten, Cortidexason, Decacort, Desamethasone, Gammacorten, Loverine, Millicorten, VisumetazoneTreatment (palbociclib, dexamethasone)

Purpose

This phase I trial studies the side effects and best dose of palbociclib when given together with dexamethasone in treating participants with B-cell acute lymphoblastic leukemia that has come back after a period of improvement or does not respond to treatment. Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone is a steroid medication that is used in combination with other medications to treat B-cell acute lymphoblastic leukemia. Giving palbociclib together with dexamethasone may work better in treating patients with B-cell acute lymphoblastic leukemia.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the dose and schedule of the combination of palbociclib and dexamethasone in
      patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL).

      ii. To determine the safety and tolerability of the combination of palbociclib and
      dexamethasone in patients with relapsed or refractory adult B-cell ALL.

      SECONDARY OBJECTIVES:

      I. To evaluate the activity of palbociclib in combination with dexamethasone in patients with
      relapsed or refractory B-cell ALL.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (palbociclib, dexamethasone)ExperimentalINDUCTION: Participants receive palbociclib PO daily and dexamethasone PO daily for 28 days in the absence of disease progression or unacceptable toxicity. Participants with disease response (M0, M1, or M2) continue to Maintenance. Patients without a disease response discontinue treatment. MAINTENANCE: Participants receive dexamethasone with a taper PO daily on days 1-7. Participants also receive palbociclib daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Palbociclib
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologic evidence of relapsed or refractory B-cell ALL

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             2 or less

          -  Philadelphia chromosome positive (Ph+) patients must be refractory to or intolerant of
             standard tyrosine kinase inhibitor therapy

          -  Patients must be able to consume oral medication

          -  Patients must have recovered to =< grade 1 or stabilized from the toxic effects of any
             prior chemotherapy (except alopecia)

          -  Creatinine clearance (CrCL) >= 60 mL/min/1.73 m^2 calculated by Cockcroft-Gault

          -  Total bilirubin < 1.5 x upper limit of normal (ULN)

          -  Negative serum or urine pregnancy test for women with child-bearing potential

          -  Patients must be able to sign consent and be willing and able to comply with scheduled
             visits, treatment plan, procedures, and laboratory testing

        Exclusion Criteria:

          -  Patients must not have evidence of active central nervous system (CNS) disease

          -  Patients must not be receiving any chemotherapy agents (except hydroxyurea);
             intrathecal methotrexate and intrathecal cytarabine are permissible

          -  Patients must not be receiving growth factors (granulocyte colony-stimulating factor
             [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]), except for
             erythropoietin

          -  Patient must not have a concurrent active malignancy for which they are receiving
             treatment.

          -  Patients with other severe concurrent disease which in the judgment of the
             investigator would make the patient inappropriate for entry into this study are
             ineligible

          -  Patients must not have received any investigational agents within 30 days of study
             entry unless they have exceeded 5 terminal half-lives of the previous study drug used
             for treatment

          -  Patients must not be pregnant or breastfeeding; pregnancy tests must be obtained for
             all females of child-bearing potential within 10 days prior to enrollment; males or
             women of childbearing potential may not participate unless they have agreed to use an
             effective contraceptive method (defined as hormonal contraceptives, intrauterine
             devices, surgical contraceptives, or condoms)

          -  Patients who have uncontrolled infection are not eligible; patients must have any
             active infections under control; fungal disease must have been adequately treated for
             at least 2 weeks before study entry; subjects with bacteremia must have documented
             negative blood cultures prior to study entry

          -  Patients who are candidates for allogeneic transplantation, have a suitable donor, and
             are willing to undergo transplantation

          -  Patients who are eligible for and willing to receive treatment with tisagenlecleucel.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLT) of the combination of palbociclib and dexamethasone
Time Frame:Up to 28 days after discontinuation of palbociclib and dexamethasone
Safety Issue:
Description:Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 should be used for grading.

Secondary Outcome Measures

Measure:Clinically relevant responses to therapy determined by bone marrow biopsy
Time Frame:Up to 1 year
Safety Issue:
Description:Response rate defined as the proportion of patients who achieve an M, M1, or M2 response will be estimated along with a 95% confidence interval.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

Last Updated

April 5, 2019