Ribociclib in Combination with Everolimus and Dexamethasone in Treating Children and Young Adults with Relapsed or Refractory Acute Lymphoblastic Leukemia

Active:	No
Cancer Type:	Leukemia	NCT ID:	NCT03740334
Trial Phases:	Phase I	Protocol IDs:	18-328 (primary) NCI-2019-01764
Eligibility:	365 Days - 30 Years, Male and Female	Study Type:	Treatment
Study Sponsor:	Dana-Farber Harvard Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT03740334

Summary

This phase I trial studies the best dose and side effects of ribociclib when given with everolimus and dexamethasone, and to see how well they work in treating children and young adults with acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Ribociclib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Anti-inflammatory drugs, such as dexamethasone lower the body’s immune response and are used with other drugs in the treatment of some types of cancer. Giving ribociclib together with everolimus and dexamethasone may work as a possible treatment for relapsed or refractory acute lymphoblastic leukemia.

Objectives

PRIMARY OBJECTIVES:
I. To determine the pharmacokinetic (PK) parameters of ribociclib in combination with dexamethasone in pediatric and young adult patients with relapsed/refractory ALL. (Cohort A)
II. To describe the toxicities of this combination in this patient population. (Cohort A)
III. To determine the dose limiting toxicities and maximum tolerated dose or recommended dose for expansion (RDE) of ribociclib in combination with everolimus and dexamethasone in pediatric and young adult patients with relapsed/refractory ALL. (Cohort B)
IV. To determine the PK parameters of ribociclib in combination with everolimus and dexamethasone in this population. (Cohort B)
V. To further explore the safety and tolerability of ribociclib in combination with everolimus and dexamethasone in pediatric and young adult patients with relapsed/refractory ALL. (Cohort C)
VI. To determine the PK parameters of ribociclib in combination with everolimus and dexamethasone in this population. (Cohort C)

SECONDARY OBJECTIVE:
I. To describe the preliminary anti-leukemic activity of the combinations of ribociclib, everolimus and dexamethasone.

EXPLORATORY OBJECTIVES:
I. To evaluate the pharmacodynamic effects of these regimens in peripheral blood and bone marrow samples.
II. To evaluate biomarkers of response to the combination of ribociclib, everolimus and dexamethasone in patients with relapsed acute lymphoblastic leukemia.

OUTLINE: This is a dose-escalation study of ribociclib. Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients receive ribociclib orally (PO) daily on days 1-21 and dexamethasone intravenously (IV) or PO twice daily (BID) on days 1-5 and 11-15. Patients also receive intrathecal chemotherapy including methotrexate, cytarabine, and hydrocortisone on day 1. Patients with central nervous system (CNS)2 disease at the start of a cycle receive intrathecal chemotherapy again on day 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

COHORT B: Patients receive everolimus PO once daily (QD) on days 1-21. Patients also receive ribociclib, dexamethasone, and intrathecal chemotherapy as in Cohort A. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, 1 year, and 2 years.

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