Treatment With Combination Chemotherapy for Relapsed or Refractory Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT03515200|
Recruitment Status : Recruiting
First Posted : May 3, 2018
Last Update Posted : June 24, 2019
Leukemia cells grow and divide fast and out of control. In normal cells, certain proteins called CDK4 and CDK6 control cell growth. The study drug called palbociclib works by blocking the CDK4 and CDK6 proteins. Palbociclib has been shown to kill leukemia cells in the laboratory and in animal studies. Palbociclib will be added to other chemotherapy drugs, such as dexamethasone, that are known to be effective in treating childhood ALL.
This study will be done in two parts: Part 1: Dose Escalation and Part 2: Dose Expansion. The goal of Part 1 of the study is to find the highest tolerable combination of palbociclib and chemotherapy that the investigators can give to patients with leukemia. Once those doses are determined, the investigators will enroll patients on Part 2: Dose Expansion. This phase will enroll additional patients that receive the highest tolerated dose of palbociclib as determined in part 1, in order to better understand the side effects and how effective this treatment approach is.
With this research study, the investigators hope to meet the following goals:
- To find the highest tolerable dose of palbociclib in combination with chemotherapy that can be given without causing severe side effects;
- To learn what kind of side effects palbociclib in combination with chemotherapy may have; and
- To learn more about the biology effects of palbociclib on the cells in the participant's body.
Up to 40 children, adolescents and young adults will participate in both parts of this study at St. Jude only.
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia, in Relapse Acute Lymphoblastic Leukemia With Failed Remission||Drug: Palbociclib Oral Capsule Drug: Intrathecal Triple Therapy Given IT Drug: Dexamethasone Drug: Bortezomib Drug: Dasatinib Drug: Doxorubicin||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
Palbociclib will be administered orally on Days 1-5, and 11-15 concurrently with dexamethasone of each 30 day cycle for one cycle (dose escalation) or up to 3 cycles for responders (dose expansion). Bortezomib will be given on Days 7, 10, 17 and 20. Doxorubicin will be given on Days 7 and 17.
Patients with Ph-like or Ph+ ALL will receive the tyrosine kinase inhibitor (TKI), dasatinib, beginning on Day 7.
Triple intrathecal chemotherapy (MHA) will be given on Day 1 of the course. The frequency and total number of IT MHA is based on the patient's level of CNS disease.
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Palbociclib in Combination With Chemotherapy in Pediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia|
|Actual Study Start Date :||April 20, 2018|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||September 2022|
This study will be done in two parts: Part 1: Dose escalation and Part 2: Dose expansion.
In Part 1 - Dose escalation: Patients that lack Ph+ or Ph-like ALL, Palbociclib, initially at 50mg/m2/day, 40% of the adult MTD, will be administered on Days 1-5 and 11-15, and escalated based on tolerability.
For patients that are Ph+ or have Ph-like ALL that are also receiving Dasatinib, Palbociclib, initially at 75mg/m2/day, 60% of the adult MTD, will be administered on Days 1-5 and 11-15 and escalated based on tolerability.
In Part 2 - Dose expansion: After determination of dose in Part 1, an additional 10 patients will be enrolled to confirm tolerability.
Drug: Palbociclib Oral Capsule
Other Name: Ibrance
Drug: Intrathecal Triple Therapy Given IT
Given intravenously (IV) or intrathecally (IT).
Other Name: Decadron
Given intravenously (IV).
Other Name: Velcade
Other Name: Sprycel®
Given intravenously (IV).
Other Name: Adriamycin®
- Maximum tolerated dose (MTD) of palbociclib plus chemotherapy [ Time Frame: End of cycle 1 (day 40 of therapy) ]Determine a tolerable combination of palbociclib plus chemotherapy in pediatric patients with relapsed or refractory ALL.
- Treatment response [ Time Frame: During the dose expansion phase, following completion of chemotherapy doses and prior to the subsequent course up to 3 cycles, if applicable (each cycle is 30 days) ]percentage of patients who attain complete remission (CR)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03515200
|Contact: Tanja A. Gruber, MD, PhDfirstname.lastname@example.org|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Tanja A. Gruber, MD, PhD 866-278-5833 email@example.com|
|Principal Investigator: Tanja A. Gruber, MD, PhD|
|Principal Investigator:||Tanja A. Gruber, MD, PhD||St. Jude Children's Research Hospital|