RELPALL: Phase I Study of Palbociclib with Chemotherapy in Children with Acute Lymphoblastic Leukemia

Phase I Study of Palbociclib in Combination with Chemotherapy in Pediatric Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia


Leukemia / Lymphoma

Diseases Treated:

Acute lymphoblastic leukemia

Eligibility Overview:

  • Younger than 22 years old
  • Diagnosis of relapsed or refractory acute lymphoblastic leukemia (ALL)
  1. Brief Summary

    While overall survival for children with acute lymphoblastic leukemia (ALL) has reached more than 90%, outcomes are poorer for children with relapsed disease.

    Many relapse studies in childhood leukemia have shifted from single agent trials to those evaluating the activity of novel agent(s) in combination with standard chemotherapy drugs. The challenge of investigating novel agents in combination with chemotherapy is to identify and select combinations that are synergistic and avoid combinations that result in unacceptable toxicity.

    Palbociclib is a reversible inhibitor of cyclin-dependent kinase 4 (CDK4) and the closely related cyclin-dependent kinase 6 (CDK6). The drug has shown high anti-leukemic activity in several pre-clinical models. The mechanism of palbociclib, which reversibly arrests cells in the G1 phase, suggests combination treatment, as opposed to single agent treatment, will be more likely to provide clinical benefit.

    Timing of combination treatment with standard cytotoxic chemotherapy drugs that kill actively dividing cells is important to maximize the chance of activity. This study will build on prior multiple myeloma experience with palbociclib in combination with dexamethasone and bortezomib while tailoring the treatment to relapsed and refractory childhood ALL through the addition of doxorubicin, and in patients with kinase targetable lesions, dasatinib or ruxolitinib.

    Primary Objective

    • Determine the maximum tolerated combination (MTC) of palbociclib plus chemotherapy in children with relapsed or refractory ALL

    Eligibility Criteria

    Inclusion criteria include:

    • Younger than 22 years old
    • Diagnosis of ALL that meets at least one of the following criteria:
      • Relapsed or refractory to chemotherapy as defined by ≥5% leukemic blasts in the bone marrow OR
      • Relapsed after hematopoietic stem cell transplantation (HSCT)
    • Karnofsky or Lansky performance score is ≥50%
    • If relapsed on therapy other than standard ALL maintenance, patient must have fully recovered from acute toxic effects of prior anti-cancer therapy
    • At least 14 days elapsed since completion of cytotoxic therapy, with the exception of standard maintenance therapy and steroids

    Exclusion Criteria include:

    • Isolated central nervous system (CNS) disease or isolated testicular disease
    • Concurrent chemotherapy or targeted anti-cancer agents, other than intrathecal therapy
    • Unresponsive to previous treatment with bortezomib or other proteasome inhibitors
    • Prior treatment with palbociclib or other CDK4/6 inhibitors
    • Pregnancy

    Study Sites

    St. Jude Children’s Research Hospital, Memphis, Tennessee

  2. About this study

    This clinical trial will test a new drug called palbociclib to treat advanced acute lymphoblastic leukemia, also known as ALL. ALL is the most common type of childhood cancer.

    Leukemia cells grow and divide fast and out of control. In normal cells, certain proteins called CDK4 and CDK6 control cell growth. Palbociclib works by blocking the CDK4 and CDK6 proteins. This drug has been approved by the U.S. Food and Drug Administration (FDA) to treat adults with breast cancer. It has not approved the drug for children with ALL.

    In this study, researchers will give palbociclib with standard chemotherapy drugs to treat ALL that did not respond to treatment (refractory) or came back after treatment (relapsed). Children, adolescents and young adults may be eligible to participate.

    Purpose of this clinical trial

    The main goal of this study is to find out if this drug is safe for children, adolescents and young adults when combined with standard chemotherapy for ALL. Researchers also want to learn more about the good and bad effects of the drug.

    Eligibility overview

    • Younger than 22 years old
    • Diagnosis of relapsed or refractory ALL
  3. RELPALL Quick View
    Sponsors St. Jude Children’s Research Hospital identifier NCT03515200
    Trial Start Date April 2018
    Estimated Enrollment 40
    Study Type Interventional
    Study Phase Phase I
    Conditions Acute Lymphoblastic Leukemia
    Ages Younger than 22 years old
    Principal investigator Tanja Gruber, MD
    Study sites St. Jude Children’s Research Hospital 
    For a consultation or to discuss RELPALL St. Jude Physician/Patient Referral Office

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.

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