Acute Lymphoblastic Leukemia, PediatricPhase 1NCT04996160
Palbociclib in Combo w/Chemotherapy in Peds Relapsed/Refractory Acute Lymphoblastic Leukemia
A Phase 1 study testing Palbociclib, Dexamethasone and Bortezomib in people with Acute Lymphoblastic Leukemia, Pediatric and Relapsed Acute Lymphoblastic Leukemia, run by Tanja Andrea Gruber at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Pediatric, Relapsed Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia
- What is being tested?
- Palbociclib, Dexamethasone and Bortezomib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jul 2021to 16 Oct 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- Subjects who relapse on therapy other than standard ALL maintenance must have fully recovered from the acute toxic effects of all prior anti cancer therapy, defined as resolution of all such toxicities to ≤ Grade 2 or lower per the inclusion/exclusion criteria prior to entering this study.
- 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 3 half lives must have elapsed since prior therapy that included a monoclonal antibody with the exception of blinatumomab. Subjects must have been off blinatumomab infusion for at least 7 days and all drug related toxicity must have resolved to Grade 2 or lower as outlined in the inclusion/exclusion criteria.
- 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%.
- No evidence of acute pulmonary infiltrates on chest radiograph
- Adequate central nervous system (CNS) function defined as
- Subjects with seizure disorder may be enrolled if on allowed anti convulsants and well controlled. Benzodiazepines and gabapentin are acceptable.
- CNS toxicity < Grade 2
- Adequate peripheral nervous system (PNS) function defined as PNS toxicity < Grade 2
Who cannot join
- Extramedullary disease status: subjects with isolated CNS disease or isolated testicular disease are not eligible.
- Concurrent chemotherapy or targeted anti cancer agents, other than intrathecal therapy.
- Subjects who have previously received bortezomib or other proteasome inhibitors that did not have a response while receiving the inhibitor are not eligible. Subjects that responded but had a subsequent relapse are eligible.
- Subjects who have previously received palbociclib or other CDK4/6 inhibitors are not eligible.
- Subject with concurrent severe and/or uncontrolled medical conditions that, in the opinion of the investigator, may impair participation in the study or the evaluation of safety and/or efficacy.
- Subjects that have an active, uncontrolled infection are not eligible.
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- Known HIV infection or active hepatitis B (defined as hepatitis B surface antigen-positive) or C (defined as hepatitis C antibody-positive).
- Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment).
- Male or female participant of reproductive potential must agree to use appropriate methods of contraception for the duration of study treatment and for at least 30 days after last dose of protocol treatment.
- Cumulative anthracyclines must not be projected to exceed 450 mg/m2 doxorubicin equivalents following completion of treatment on protocol. Therefore, for subjects receiving one course on protocol cumulative anthracyclines cannot exceed 400 mg/m2 doxorubicin equivalents at the time of enrollment (≤ 200 mg/m2 doxorubicin equivalents for subject with prior radiation therapy to the mediastinum).
- Inability or unwillingness or research participant or legal guardian/representative to give written informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lucile Packard Children's Hospital Stanford
Stanford, California, 94304
About this study
Official title: A Phase I Study at Stanford of Palbociclib in Combination With Chemotherapy in Pediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (RELPALL2)
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
Read the detailed description
Primary objective: To confirm the safety of the previously estimated MTD of 100 mg/m2/daily palbociclib on Days 1 to 5; 11 to 15; and 21 to 30, in combination with chemotherapy, on the basis of observed DLTs for pediatric relapsed ALL patients that do not have Ph+ and Ph like mutations (Cohort 1), and to determine the MTD of palbociclib in combination with chemotherapy and kinase inhibition in pediatric relapsed ALL patients with Ph+ and Ph like subtypes (Cohort 2).
Secondary objective: To estimate the overall response rate (ORR) to the combination of palbociclib and chemotherapy in pediatric subjects with relapsed or refractory ALL that does not carry Ph+ or Ph like mutations (Cohort 2).
- Conditions
- Acute Lymphoblastic Leukemia, Pediatric, Relapsed Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia
- Being tested
- Palbociclib, Dexamethasone, Bortezomib, Doxorubicin
- Keywords
- ALL, Relapsed ALL
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PalbociclibDrug
Also called 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
Oral
DexamethasoneDrug
Also called dexamethasone intensol
8 mg/m2/day divided BID, PO, NG, or IV
BortezomibDrug
1.3 mg/m2/dose, IV (preferred) or SC
DoxorubicinDrug
Also called doxorubicin.HCl
25 mg/m2/dose IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Palbociclib; Drug: Dexamethasone; Drug: Bortezomib; Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: within 30 days from last treatment with palbociclib.
Secondary outcomes (1)
Overall response rate (ORR)
The efficacy of the combination of palbociclib and chemotherapy with kinase inhibition will be assessed as the overall clinical response rate of subjects treated at the MTD, consisting of those with complete remission (CR); complete remission morphologic (CRM); and partial response (PR), defined as the flow cytometric results below.
- CR: minimal residual disease (MRD) in bone marrow < 0.01% ("MRD-negative").
- CRM: minimal residual disease (MRD) in bone marrow 0.01% to 5%.
- PR: Decrease of at least 50% in the percentage of blasts and 5% to 25% blasts. The outcome will be reported as the number of participants Cohorts 1 and 2 with a clinical response, a number without dispersion. Results for Cohort 2 may be stratified by dose level administered.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2021
- Study start9 Jul 2021
- Primary completion16 Oct 2023
- Study completion16 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukemia, PediatricStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tanja Andrea Gruber
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Tanja Andrea Gruber, Stanford University
- Investigators
- Tanja A Gruber, MD, Principal investigator, Stanford Universiy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04996160
- Sponsor's protocol ID
- IRB-60392
- Other IDs
- NCI-2021-09313
- Status last verified
- Apr 2026
- First submitted
- 22 Jul 2021
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study at Stanford of Palbociclib in Combination With Chemotherapy in Pediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (RELPALL2)
- ClinicalTrials.gov ID
- NCT04996160
- Acronym / sponsor ID
- IRB-60392
- Conditions
- Acute Lymphoblastic Leukemia, Pediatric, Relapsed Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia
- Keywords
- ALL, Relapsed ALL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Tanja Andrea GruberUniversity, hospital or other
- Study start
- 9 Jul 2021 (actual)
- Primary completion
- 16 Oct 2023 (actual)
- Study completion
- 16 Oct 2023 (actual)
- First posted
- 9 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Primary objective: To confirm the safety of the previously estimated MTD of 100 mg/m2/daily palbociclib on Days 1 to 5; 11 to 15; and 21 to 30, in combination with chemotherapy, on the basis of observed DLTs for pediatric relapsed ALL patients that do not have Ph+ and Ph like mutations (Cohort 1), and to determine the MTD of palbociclib in combination with chemotherapy and kinase inhibition in pediatric relapsed ALL patients with Ph+ and Ph like subtypes (Cohort 2).
Secondary objective: To estimate the overall response rate (ORR) to the combination of palbociclib and chemotherapy in pediatric subjects with relapsed or refractory ALL that does not carry Ph+ or Ph like mutations (Cohort 2).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 -(without Ph+ / Ph like mutation) | Experimental | Drug: Palbociclib, Drug: Dexamethasone, Drug: Bortezomib, Drug: DoxorubicinDose 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. |
| Cohort 2-(Ph+ / Ph like ALL subtypes): | Experimental | Drug: Palbociclib, Drug: Dexamethasone, Drug: Bortezomib, Drug: DoxorubicinDose 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. |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- Participants must have a diagnosis of acute lymphoblastic leukemia and disease meets at least one of the following criteria:
- Prior Treatment:
- 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:
Key exclusion criteria (11 listed)
- Extramedullary disease status: subjects with isolated CNS disease or isolated testicular disease are not eligible.
- Concurrent chemotherapy or targeted anti cancer agents, other than intrathecal therapy.
- Subjects who have previously received bortezomib or other proteasome inhibitors that did not have a response while receiving the inhibitor are not eligible. Subjects that responded but had a subsequent relapse are eligible.
- Subjects who have previously received palbociclib or other CDK4/6 inhibitors are not eligible.
- Subject with concurrent severe and/or uncontrolled medical conditions that, in the opinion of the investigator, may impair participation in the study or the evaluation of safety and/or efficacy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PalbociclibAlso: 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)-oneOral | Drug | Cohort 1 -(without Ph+ / Ph like mutation), Cohort 2-(Ph+ / Ph like ALL subtypes): |
| DexamethasoneAlso: dexamethasone intensol8 mg/m2/day divided BID, PO, NG, or IV | Drug | Cohort 1 -(without Ph+ / Ph like mutation), Cohort 2-(Ph+ / Ph like ALL subtypes): |
| Bortezomib1.3 mg/m2/dose, IV (preferred) or SC | Drug | Cohort 1 -(without Ph+ / Ph like mutation), Cohort 2-(Ph+ / Ph like ALL subtypes): |
| DoxorubicinAlso: doxorubicin.HCl25 mg/m2/dose IV | Drug | Cohort 1 -(without Ph+ / Ph like mutation), Cohort 2-(Ph+ / Ph like ALL subtypes): |
Primary outcome
Dose-limiting Toxicity (DLT)
Time frame: within 30 days from last treatment with palbociclib.
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.
1 secondary outcome
Overall response rate (ORR)
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tanja A Gruber, MD principal investigator
Stanford Universiy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Palbociclib, Dexamethasone and Bortezomib in people with Acute Lymphoblastic Leukemia, Pediatric and Relapsed Acute Lymphoblastic Leukemia, run by Tanja Andrea Gruber at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting Toxicity (DLT) (time frame: within 30 days from last treatment with palbociclib.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.