Recurrent B Acute Lymphoblastic Leukemia, Refractory B Acute Lymphoblastic Leukemia
Conditions
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.
Interventions
DRUGPalbociclib
Given PO
DRUGDexamethasone
Given PO
Sponsors
Pfizer
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicities (DLT) of the combination of palbociclib and dexamethasone | 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 | Up to 28 days after discontinuation of palbociclib and dexamethasone | CTCAE version 4.03 should be used for grading. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically relevant responses to therapy determined by bone marrow biopsy | 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. |
Countries
United States
Outcome results
None listed