Ribociclib in Combination With Everolimus and Dexamethasone in Relapsed ALL

Running, not enrolling · Phase 1

Conditions studied: Acute Lymphoblastic Leukemia ALL

In brief

This research study is evaluating a drug called ribociclib (LEE011) given in combination with everolimus and other standard of care chemotherapy drugs as a possible treatment for relapsed or refractory ALL. The names of the drugs involved in this study are: * ribociclib * everolimus * dexamethasone

Key facts

Study ID

NCT03740334

Run by

Dana-Farber Cancer Institute

People needed

45

Starts

2019-01-30

Expected to finish

2026-10-01

Last updated by the study team

2025-11-21

Who can join

Age: 1 and older, up to 30. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age > 12 months (365 days) and ≤ 30 years
• Histologically confirmed diagnosis of either 1) relapsed or refractory ALL or 2) CML in lymphoid blast crisis (must have failed at least 2 lines of TKI therapy)
• Primary refractory disease: Persistent disease after at least two induction attempts
• Relapsed disease: Second or subsequent relapse, or any relapse refractory to salvage chemotherapy
• Participants must have bone marrow with ≥ 1% lymphoblasts definitively identified either on a bone marrow aspirate or biopsy sample, as assessed by morphology, immunohistochemical studies, flow cytometry, karyotype, cytogenetic testing such as fluorescent in situ hybridization (FISH) or other molecular studies.
• Participants with CNS1 or CNS2 disease are eligible. Patients with isolated CNS relapse or CNS 3 disease are not eligible. (Refer to Section 12.4 for definitions of CNS status)
• Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet all of the following criteria:
• Corticosteroids: 14 days must have elapsed since the completion of systemic corticosteroid administration. The following uses of corticosteroids are permitted: single doses (e.g., during anesthesia), topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airway diseases, asthma), eye drops or local injections (e.g., intra-articular)
• Myelosuppressive chemotherapy: 14 days must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications within 14 days without a "wash-out" period:
• Standard maintenance therapy, other than corticosteroids (vincristine, 6MP, low dose methotrexate)
• Hydroxyurea
• Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine.
• Radiation therapy (XRT):
• Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry
• XRT for chloroma does not require a washout period.
• Palliative XRT does not require a washout
• Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.
• Immunotherapy: At least 6 weeks after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy or checkpoint inhibitors.
• Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody. (See table on DVL homepage listing monoclonal antibody half-lives: https://members.childrensoncologygroup).
• Prior hematopoietic stem cell transplant (HSCT): Patients who have received HSCT are eligible, but must meet all of the following conditions:
• Autologous HSCT > 60 days of study entry
• Allogeneic HSCT > 90 days of study entry
• No evidence of graft-versus-host-disease (GVHD)
• Weaning or stable doses of calcineurin inhibitors are permitted provided there is no evidence of active GVHD.
• Participants must have a body surface area (BSA) ≥ 0.4 m2.

You may not qualify if…

• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ribociclib, everolimus or dexamethasone (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Individuals with CNS 3 leukemia at time of study entry. History of CNS 3 disease is allowable as long as patient meets eligibility criteria (CNS 1 or 2) at time of enrollment.
• Individuals with Down syndrome.
• Treatment with hematopoietic growth factors (G-CSF):
• Long-acting (e.g., Neulasta) within 14 days prior to study entry
• Short-acting (e.g., Neupogen) within 7 days prior to study entry
• Treatment with an investigational agent within 28 days of study entry, or 3 half-lives, whichever is longer.
• Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Cardiomyopathy
• Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure or history of significant/symptomatic bradycardia.
• Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication (See Appendix C for list of prohibited medications)
• Inability to determine the QTcF interval on screening EKG (using Fridericia's correction)
• Prior exposure to a CDK4/6 inhibitor
• Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug (see Appendix C for prohibited medications):
• Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
• Medications with a narrow therapeutic window that are predominantly metabolized through CYP3A4/5
• Herbal preparations/medications, dietary supplements.
• Patients refractory to red blood cell or platelet transfusions.
• Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
• Patients with systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.

Where it is running

• Children's Hospital Colorado — Aurora, Colorado, United States
• Nemours/Alfred I. duPont Hospital for Children — Wilmington, Delaware, United States
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States
• Boston Children's Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• Texas Children's Hospital — Houston, Texas, United States
• Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States

Full record on ClinicalTrials.gov

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