Palbociclib in Combo w/Chemotherapy in Peds Relapsed/Refractory Acute Lymphoblastic Leukemia

NCT04996160 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-60392NCI-2021-09313
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

With this research study has following goals

• To confirm the highest tolerable dose of palbociclib in combination with chemotherapy is safe and well-tolerated.
• To learn more about side effects of palbociclib in combination with chemotherapy;
• To learn more about the biological effects of palbociclib on the cells in your body

Conditions

Acute Lymphoblastic Leukemia, Pediatric; Relapsed Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia

Keywords

ALL; Relapsed ALL

Outcome Measures

Primary Outcomes (1)

• Dose-limiting Toxicity (DLT)

  The primary outcome for this study, for the purposes of Clinical Trials.gov registration and results reporting, is dose-limiting toxicities (DLTs) experience by subjects without the Ph+ / Ph-like mutation (Cohort 1), and those with the Ph+ / Ph-like mutation (Cohort 2). The outcome will be reported for Cohorts 1 and 2 as the number of DLTs that occur within 30 days of last treatment with palbociclib. Results for Cohort 2 may be stratified by dose level administered.

  within 30 days from last treatment with palbociclib.

Secondary Outcomes (1)

• Overall response rate (ORR)

  24 months

Study Arms (2)

Cohort 1 -(without Ph+ / Ph like mutation)

EXPERIMENTAL

Dose expansion phase-10 subjects in Cohort 1, 100 mg/m2/daily palbociclib on Days 1 to 5; 11 to 15; and 21 to 30, in combination with chemotherapy. All subjects will receive palbociclib with dexamethasone, bortezomib, and doxorubicin. dexamethasone of each 30 day cycle for up to 3 cycles for responders which include complete remission, complete remission morphologic, and partial response as defined in section 10.2.1. Bortezomib will be given on Days 7, 10, 17 and 20. Doxorubicin will be given on Days 7 and 17.

Drug: Palbociclib; Drug: Dexamethasone; Drug: Bortezomib; Drug: Doxorubicin

Cohort 2-(Ph+ / Ph like ALL subtypes):

EXPERIMENTAL

Dose escalation phase- 12 subjects in Cohort 2, Palbociclib dose escalation will begin at 75 mg/m2/day, on Days 1 to 5; 11 to 15; and 21 to 30, and escalate or de escalate. All subjects will receive palbociclib with dexamethasone, bortezomib, and doxorubicin. dexamethasone of each 30 day cycle for up to 3 cycles for responders which include complete remission, complete remission morphologic, and partial response as defined in section 10.2.1. Bortezomib will be given on Days 7, 10, 17 and 20. Doxorubicin will be given on Days 7 and 17. Subjects with Ph+ / Ph-like mutation will receive a tyrosine kinase inhibitor (TKI or KI, either dasatinib or ruxolitinib).3 on 3 dose escalation with 2 dose levels.

Drug: Palbociclib; Drug: Dexamethasone; Drug: Bortezomib; Drug: Doxorubicin

Interventions

Palbociclib DRUG

Oral

Also known as: Ibrance, PD-0332991, 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one

Cohort 1 -(without Ph+ / Ph like mutation); Cohort 2-(Ph+ / Ph like ALL subtypes):

Dexamethasone DRUG

8 mg/m2/day divided BID, PO, NG, or IV

Also known as: dexamethasone intensol

Cohort 1 -(without Ph+ / Ph like mutation); Cohort 2-(Ph+ / Ph like ALL subtypes):

Bortezomib DRUG

1.3 mg/m2/dose, IV (preferred) or SC

Cohort 1 -(without Ph+ / Ph like mutation); Cohort 2-(Ph+ / Ph like ALL subtypes):

Doxorubicin DRUG

25 mg/m2/dose IV

Also known as: doxorubicin.HCl

Cohort 1 -(without Ph+ / Ph like mutation); Cohort 2-(Ph+ / Ph like ALL subtypes):

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must have a diagnosis of acute lymphoblastic leukemia and disease meets at least one of the following criteria:
• relapsed or refractory to chemotherapy as defined by ≥ 5% leukemic blasts in the bone marrow or flow cytometry confirmed leukemic blasts in the peripheral blood
• relapsed after hematopoietic stem cell transplantation (HSCT)
• Subjects must have had histologic, morphologic or flow cytometric verification of the malignancy at relapse
• Prior Treatment:
• Subjects who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study.

You may not qualify if:

• At least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of standard maintenance therapy and steroids.
• At least 7 days must have elapsed since completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur.
• At least 42 days must have elapsed since CAR T cell therapy.
• At least 90 days have elapsed since bone marrow transplant and participant is off immune suppression for \> 2 weeks, if applicable with no evidence of active GVHD.
• At least 2 weeks must have elapsed since local XRT (small port); ≥ 3 months must have elapsed if prior cranial or craniospinal XRT was received, if ≥ 50% of the pelvis was irradiated, or if TBI was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
• Participants must be \< 25 years of age.
• Karnofsky or Lansky performance score is \> 50% (corresponding to ECOG Score of \< 2). The Lansky performance score should be used for participants \< 16 years and the Karnofsky performance score for participants ≥ 16 years (see Appendix D). Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Adequate renal function defined as glomerular filtration rate \> 60 mL/min/1.73 m2 or serum creatinine based on age as follows:
• Max serum creatine (mg/dL) Age (years) Male Female \< 6 months 0.4 0.4 6 months to \< 1 year 0.5 0.5 1 to \< 2 years 0.6 0.6 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 \> 16 years 1.7 1.4
• Adequate hepatic function defined as
• Total bilirubin ≤ 2 x upper limit of normal (ULN) for age, and
• ALT \< 3 x ULN for age, unless elevation is due to leukemic infiltration
• Adequate cardiac function defined as shortening fraction of \> 27% or ejection fraction \> 45%.
• Adequate pulmonary function defined as
• No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94%.

Sponsors & Collaborators

• Tanja Andrea Gruber: lead

Study Sites (1)

Lucile Packard Children's Hospital Stanford

Stanford, California, 94304, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

palbociclib; Dexamethasone; Calcium Dobesilate; Bortezomib; Doxorubicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Tanja A Gruber, MD

  Stanford Universiy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chambers Family Endowed Professor for Pediatric Cancer University

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: August 9, 2021
• Study Start: July 9, 2021
• Primary Completion: October 16, 2023
• Study Completion: October 16, 2023
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)