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

• ClinicalTrials.gov Identifier: NCT03472573
• Recruitment Status: Recruiting
• First Posted: March 21, 2018
• Last Update Posted: December 8, 2020
• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborator: Pfizer
• Information provided by (Responsible Party): Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Tracking Information

• First Submitted Date: March 14, 2018
• First Posted Date: March 21, 2018
• Last Update Posted Date: December 8, 2020
• Actual Study Start Date: May 9, 2018
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2018)

• 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 ]
  Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 should be used for grading.
• Maximum tolerated dose (MTD) of the combination of palbociclib and dexamethasone defined as the highest dose level where a DLT occurs in at most one out of six patients treated [ Time Frame: Up to 28 days after discontinuation of palbociclib and dexamethasone ]
  CTCAE version 4.03 should be used for grading.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 14, 2018)

Clinically relevant responses to therapy determined by bone marrow biopsy [ Time Frame: Up to 1 year ]

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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• Brief Summary: 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Palbociclib
  Given PO
  Other Names:

  • 571190-30-2
  • 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-0332991
• Drug: Dexamethasone
  Given PO
  Other Names:

  • Baycuten
  • Cortidexason
  • Decacort
  • Desamethasone
  • Gammacorten
  • Loverine
  • Millicorten
  • Visumetazone

Study Arms

Experimental: Treatment (palbociclib, dexamethasone)

INDUCTION: 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.

Interventions:

• Drug: Palbociclib
• Drug: Dexamethasone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 14, 2018): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2022
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Margaret Kasner, MD; 215-955-8874; margaret.kasner@jefferson.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03472573
• Other Study ID Numbers: 17P.676
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

• IPD Sharing Statement: Not Provided
• Responsible Party: Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
• Study Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: Pfizer

Investigators

• Principal Investigator: Margaret Kasner, MD; Sidney Kimmel Cancer Center at Thomas Jefferson University

• PRS Account: Thomas Jefferson University
• Verification Date: December 2020