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

Primary Purpose

Recurrent B Acute Lymphoblastic Leukemia, Refractory B Acute Lymphoblastic Leukemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Palbociclib

Dexamethasone

About this trial

This is an interventional treatment trial for Recurrent B Acute Lymphoblastic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Sidney Kimmel Cancer Center at Thomas Jefferson University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (palbociclib, dexamethasone)

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities (DLT) of the combination 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

CTCAE version 4.03 should be used for grading.

Secondary Outcome Measures

Clinically relevant responses to therapy determined by bone marrow biopsy

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.

Full Information

NCT ID

NCT03472573

First Posted

March 14, 2018

Last Updated

June 2, 2022

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborators

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT03472573

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)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Completed

Study Start Date

May 9, 2018 (Actual)

Primary Completion Date

August 4, 2021 (Actual)

Study Completion Date

August 4, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborators

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent B Acute Lymphoblastic Leukemia, Refractory B Acute Lymphoblastic Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (palbociclib, dexamethasone)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Palbociclib

Other Intervention Name(s)

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

Intervention Description

Given PO

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Other Intervention Name(s)

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

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Incidence of dose limiting toxicities (DLT) of the combination of palbociclib and dexamethasone

Description

Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 should be used for grading.

Time Frame

Up to 28 days after discontinuation of palbociclib and dexamethasone

Title

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

Description

CTCAE version 4.03 should be used for grading.

Time Frame

Up to 28 days after discontinuation of palbociclib and dexamethasone

Secondary Outcome Measure Information:

Title

Clinically relevant responses to therapy determined by bone marrow biopsy

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.

Time Frame

Up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Margaret Kasner, MD

Organizational Affiliation

Sidney Kimmel Cancer Center at Thomas Jefferson University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sidney Kimmel Cancer Center at Thomas Jefferson University

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

12. IPD Sharing Statement

Links:

URL

http://hospitals.jefferson.edu/

Description

Thomas Jefferson University Hospital

Learn more about this trial

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

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