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Palbociclib and Combination Chemotherapy in Treating Pediatric Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia

Trial Status: Temporarily Closed to Accrual

This phase I trial studies how well palbociclib and combination chemotherapy work in treating pediatric patients with acute lymphoblastic leukemia that has come back or does not respond to treatment. Palbociclib, dasatinib, and ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, bortezomib, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving palbociclib and combination chemotherapy may work better in treating pediatric patients with acute lymphoblastic leukemia.

Inclusion Criteria

  • Participants must have a diagnosis of acute lymphoblastic leukemia and disease meets at least one of the following criteria: * Relapsed or refractory to chemotherapy as defined by >= 5% leukemic blasts in the bone marrow or flow cytometry confirmed leukemic blasts in the peripheral blood * Relapsed after hematopoietic stem cell transplantation (HSCT)
  • Patients must have had histologic, morphologic or flow cytometric verification of the malignancy at relapse
  • Karnofsky or Lansky performance score is >= 50% (corresponding to Eastern Cooperative Oncology Group [ECOG] score of =< 2); the Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants >= 16 years; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study
  • Patients who relapse on therapy other than standard ALL maintenance must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study
  • At least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of standard maintenance therapy and steroids
  • At least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
  • At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody with the exception of blinatumomab; patients must have been off blinatumomab infusion for at least 7 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria
  • At least 42 days must have elapsed since chimeric antigen receptor (CAR)-T cell therapy
  • At least 90 days have elapsed since bone marrow transplant and participant is off immune suppression for >= 2 weeks, if applicable with no evidence of active graft versus host disease (GVHD)
  • At least 2 weeks must have elapsed since local radiation therapy (XRT) (small port); >= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
  • Adequate renal function defined as glomerular filtration rate >= 60 cc/min/1.73 m^2 or serum creatinine based on age as follows: * Age: < 6 months; maximum serum creatinine (mg/dL): 0.4 (male, female) * Age: 6 months to < 1 year; maximum serum creatinine (mg/dL): 0.5 (male, female) * Age: 1 to < 2 years; maximum serum creatinine (mg/dL): 0.6 (male, female) * Age: 2 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male, female) * Age: 6 to < 10 years; maximum serum creatinine (mg/dL): 1 (male, female) * Age: 10 to < 13 years; maximum serum creatinine (mg/dL): 1.2 (male, female) * Age: 13 to < 16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female) * Age: >= 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female)
  • Total bilirubin =< 2 x upper limit of normal (ULN) for age
  • Alanine aminotransferase (ALT) =< 3 x ULN for age, unless elevation is due to leukemic infiltration
  • Adequate cardiac function defined as shortening fraction of >= 27% or ejection fraction >= 45%
  • No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94%
  • No evidence of acute pulmonary infiltrates on chest radiograph
  • Adequate central nervous system (CNS) function defined as: * Patients with seizure disorder may be enrolled if on allowed anti-convulsants and well controlled; benzodiazepines and gabapentin are acceptable * CNS toxicity < grade 2
  • Adequate peripheral nervous system (PNS) function defined as: * PNS toxicity < grade 2

Exclusion Criteria

  • Extramedullary disease status: patients with isolated CNS disease or isolated testicular disease are not eligible
  • Concurrent chemotherapy or targeted anti-cancer agents, other than intrathecal therapy
  • Patients who have previously received bortezomib or other proteasome inhibitors that did not have a response while receiving the inhibitor are not eligible; patients that responded but had a subsequent relapse are eligible
  • Patients who have previously received palbociclib or other CDK4/6 inhibitors are not eligible
  • Patient with concurrent severe and/or uncontrolled medical conditions that, in the opinion of the investigator, may impair participation in the study or the evaluation of safety and/or efficacy
  • Patients that have an active, uncontrolled infection are not eligible
  • Known human immunodeficiency virus (HIV) infection or active hepatitis B (defined as hepatitis B surface antigen–positive) or C (defined as hepatitis C antibody–positive)
  • Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment)
  • Male or female participant of reproductive potential must agree to use appropriate methods of contraception for the duration of study treatment and for at least 30 days after last dose of protocol treatment
  • Cumulative anthracyclines must not exceed 450 mg/m^2 doxorubicin equivalents following completion of treatment on protocol; therefore for patients receiving one course on protocol cumulative anthracyclines must be less than or equal to 400 mg/m^2 doxorubicin equivalents at the time of enrollment
  • Inability or unwillingness or research participant or legal guardian/representative to give written informed consent


Saint Jude Children's Research Hospital
Contact: Tanja Andrea Gruber
Phone: 901-319-0070


I. To determine a tolerable combination of palbociclib plus chemotherapy in pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL).


I. To estimate the overall response rate to the combination of palbociclib and chemotherapy in pediatric patients with relapsed or refractory ALL.


I. Measure cell cycle kinetics of ALL cells pre- and post-treatment with palbociclib.

II. Describe the genomic landscape of relapsed/refractory ALL patients using whole genome, whole exome, and transcriptome next generation sequencing.

III. Evaluate modes of resistance in non-responders by next generation sequencing and western blot analyses.

OUTLINE: This is a dose-escalation study of palbociclib.

Patients receive palbociclib orally (PO) or nasogastrically (NG) on days 1-5 and 11-15 (and days 21-30 for highest dose level), dexamethasone PO, NG, or intravenously (IV) twice daily (BID) on days 1-5 and 11-15, bortezomib IV or subcutaneously (SC) over 3-5 seconds on days 7, 10, 17, and 20, doxorubicin IV on days 7 and 17, and dasatinib PO or NG once daily (QD) or ruxolitinib PO or NG BID on days 7-30 in the absence of disease progression or unacceptable toxicity. Triple intrathecal (IT) therapy with methotrexate, hydrocortisone, and cytarabine (MHA) will be given on day 1 of the cycle. The frequency and total number of IT MHA is based on the patient's level of central nervous system (CNS) disease.

After completion of study treatment, patients are followed up within 30 days and 6 weeks.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Saint Jude Children's Research Hospital

Principal Investigator
Tanja A. Gruber

  • Primary ID RELPALL
  • Secondary IDs NCI-2018-00814
  • ID NCT03515200