Ribociclib in Combination With Everolimus and Dexamethasone in Relapsed ALL
Phase I Trial of Ribociclib in Combination With Everolimus and Dexamethasone in Children and Young Adults With Relapsed Acute Lymphoblastic Leukemia
1 other identifier
interventional
45
1 country
12
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2019
Longer than P75 for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 8, 2018
CompletedFirst Posted
Study publicly available on registry
November 14, 2018
CompletedStudy Start
First participant enrolled
January 30, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 4, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2026
ExpectedNovember 21, 2025
November 1, 2025
4.1 years
November 8, 2018
November 20, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Pharmacokinetic analysis - AUC(0-24hr):
Blood samples obtained for Pharmacokinetic (PK) analysis will be used to describe how study drugs are distributed and metabolized by human subjects. Samples for PK analysis will be obtained during Cycle 1 of all Cohorts. Area under the concentration-time curve from time zero to 24 hours (AUC(0-24hr)) is a measure of a subject's exposure to study drugs.
3 years
Pharmacokinetic analysis - Cmax
Blood samples obtained for Pharmacokinetic (PK) analysis will be used to describe how study drugs are distributed and metabolized by human subjects. Samples for PK analysis will be obtained during Cycle 1 of all Cohorts. Maximum observed concentration (Cmax) will be determined from the plasma concentration data
3 years
Pharmacokinetic analysis - Tmax
Blood samples obtained for Pharmacokinetic (PK) analysis will be used to describe how study drugs are distributed and metabolized by human subjects. Samples for PK analysis will be obtained during Cycle 1 of all Cohorts. Time of first observation of Cmax (tmax) will be determined from the plasma concentration data
3 years
Toxicity assessments
Toxicities experience by study subjects will be reported and graded for severity using CTCAE version 5. These data will contribute to determining the Maximum tolerated dose (MTD)
3 years
Maximum Tolerated Dose (MTD)
This dose, determined by review of toxicity data, will define the highest dose that is tolerable in this patient population.
3 years
Secondary Outcomes (1)
Overall Response Rate (ORR)
3 years
Study Arms (3)
Ribociclib (RIBO) + Dexamethasone (DEX)
EXPERIMENTAL* Ribociclib administered daily for 21 consecutive days * Dexamethasone administered intravenously on days 1-5 and again on days 11-15
RIBO + Everolimus (EVE) + DEX
EXPERIMENTAL* Ribociclib administered daily for 21 consecutive days * Dexamethasone administered intravenously on days 1-5 and again on days 11-15 * Everolimus administered daily for 21 consecutive days
RIBO + EVE+ DEX (dose expansion)
EXPERIMENTAL* Ribociclib administered daily for 21 consecutive days. Dosing at RDE * Dexamethasone administered intravenously on days 1-5 and again on days 11-15 * Everolimus administered daily for 21 consecutive days. Dosing at RDE
Interventions
Ribociclib, blocks a specific type of protein called a cyclin-dependent kinases (CDK)
Corticosteroids are commonly used to treat ALL.
Everolimus is an inhibitor of mTOR. mTOR inhibition blocks the translation of genes that regulate cancer cell proliferation
Eligibility Criteria
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.
- +23 more criteria
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.
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dana-Farber Cancer Institutelead
- Novartiscollaborator
Study Sites (12)
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Nemours/Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10174, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew E Place, MD, PhD
Dana-Farber Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
November 8, 2018
First Posted
November 14, 2018
Study Start
January 30, 2019
Primary Completion
March 4, 2023
Study Completion (Estimated)
October 1, 2026
Last Updated
November 21, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication.
- Access Criteria
- Requests may be directed to: \[contact information for Sponsor-Investigator or designee\].
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor-Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.