Clinical trial NCT03472573: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Recurrent B Acute Lymphoblastic Leukemia
Refractory B Acute Lymphoblastic Leukemia
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2018-03-21
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLT) of the combination of palbociclib and dexamethasone
timeFrame: Up to 28 days after discontinuation of palbociclib and dexamethasone
measure: 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
timeFrame: Up to 28 days after discontinuation of palbociclib and dexamethasone
Secondary outcomes:
measure: Clinically relevant responses to therapy determined by bone marrow biopsy
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center at Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Sidney Kimmel Cancer Center at Thomas Jefferson University
name: Margaret Kasner, MD
role: PRINCIPAL_INVESTIGATOR
References: