Palbociclib + Chemotherapy for Acute Lymphoblastic Leukemia
Recruiting in Palo Alto (17 mi)
Overseen ByTanja A Gruber, MD
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Tanja Andrea Gruber
Must not be taking: Proteasome inhibitors, CDK4/6 inhibitors
Disqualifiers: Isolated CNS/testicular disease, uncontrolled infection, others
No Placebo Group
Breakthrough Therapy
Approved in 4 jurisdictions
Trial Summary
What is the purpose of this trial?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
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, it mentions that participants must have recovered from the effects of previous cancer treatments and meet certain time requirements since their last treatments. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug Palbociclib for treating acute lymphoblastic leukemia?
A phase I study suggests that combining Palbociclib with dexamethasone may help target the growth of leukemia cells in patients with relapsed or hard-to-treat B-cell acute lymphoblastic leukemia.
12345Is Palbociclib safe for humans?
A phase I study explored the safety of Palbociclib combined with dexamethasone for treating relapsed or refractory B-cell acute lymphoblastic leukemia, indicating it has been tested in humans for safety.
16789How is the drug palbociclib unique in treating acute lymphoblastic leukemia?
Palbociclib is unique because it is a CDK4/6 inhibitor, which means it targets specific proteins that help cancer cells grow, and it is being studied in combination with chemotherapy to improve outcomes for patients with relapsed or refractory acute lymphoblastic leukemia, a condition where standard treatments often fail.
1251011Eligibility Criteria
This trial is for children and young adults under 25 with acute lymphoblastic leukemia that's come back or didn't respond to treatment. They should be off certain medications, have no severe infections, and not be pregnant. Participants need functioning major organs and a minimum performance score indicating they can do daily activities.Inclusion Criteria
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
Subjects must have had histologic, morphologic or flow cytometric verification of the malignancy at relapse
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Exclusion Criteria
Extramedullary disease status: subjects with isolated CNS disease or isolated testicular disease 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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Participant Groups
The study tests the highest dose of palbociclib (a cancer drug) that's safe when given with chemotherapy in young patients with leukemia. It aims to understand the side effects and how this drug affects cancer cells in the body.
2Treatment groups
Experimental Treatment
Group I: Cohort 2-(Ph+ / Ph like ALL subtypes):Experimental Treatment4 Interventions
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.
Group II: Cohort 1 -(without Ph+ / Ph like mutation)Experimental Treatment4 Interventions
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.
Palbociclib is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Ibrance for:
- HR-positive, HER2-negative advanced or metastatic breast cancer
🇪🇺 Approved in European Union as Ibrance for:
- HR-positive, HER2-negative locally advanced or metastatic breast cancer
🇨🇦 Approved in Canada as Ibrance for:
- HR-positive, HER2-negative advanced or metastatic breast cancer
🇯🇵 Approved in Japan as Ibrance for:
- HR-positive, HER2-negative advanced or recurrent breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Lucile Packard Children's Hospital StanfordStanford, CA
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Who Is Running the Clinical Trial?
Tanja Andrea GruberLead Sponsor
Stanford UniversityLead Sponsor
References
A phase I study of the combination of palbociclib and dexamethasone for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia. [2023]Despite advances in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), outcomes for relapsed/refractory (R/R) disease remain poor. Preclinical studies suggest that the combination of the CDK4/6 inhibitor palbociclib and dexamethasone may be effective in targeting leukemic cell growth. We conducted a phase I study of escalating doses of palbociclib in combination with dexamethasone in adults with R/R B-ALL.
Progress and challenges in the therapy of adult acute lymphoblastic leukemia. [2019]Acute lymphoblastic leukemia is a heterogeneous disease with distinct biologic and prognostic groupings. Although current therapies result in high complete remission rates, long-term disease-free survival rates have remained disappointingly low. Results from recent studies using risk-tailored approaches suggest improvement in overall survival for high-risk groups, such as those with Philadelphia chromosome-positive acute lymphoblastic leukemia. Furthermore, the incorporation of imatinib mesylate into the treatment regimen for Philadelphia chromosome-positive acute lymphoblastic leukemia patients may lead to better outcomes. Finally, quantification of minimal residual disease at various time points during therapy is being investigated as a means to predict more accurately a patient's response to therapy, and to make therapeutic decisions.
Optimizing the treatment of acute lymphoblastic leukemia in younger and older adults: new drugs and evolving paradigms. [2022]In the past decade, the available treatments for patients with acute lymphoblastic leukemia (ALL) have rapidly expanded, in parallel with an increased understanding of the genomic features that impact the disease biology and clinical outcomes. With the development of the anti-CD22 antibody-drug conjugate inotuzumab ozogamicin, the CD3-CD19 bispecific T-cell engager antibody blinatumomab, CD19 chimeric antigen receptor T-cell therapy, and the potent BCR-ABL1 tyrosine kinase inhibitor ponatinib, the outlook of ALL in both younger and older adults has substantially improved. The availability of highly effective drugs raised important questions concerning the optimal combination and sequence of these agents, their incorporation into frontline regimens, and the role of hematopoietic stem cell transplantation. In this review, we discuss the rapidly evolving paradigms in the treatment of ALL, highlighting both established and effective regimens, as well as promising new therapies that are being evaluated in ongoing clinical trials. We specifically focus on novel combination regimens in both the frontline and salvage settings that are leading to new standards of care in the treatment of ALL.
Immunotherapy approaches to treat adult acute lymphoblastic leukemia. [2017]Recent developments in immunotherapy are improving treatment results of B-precursor acute lymphoblastic leukemia. This advancement is promoted by new monoclonal antibodies such as inotuzumab ozogamicin, ofatumumab and blinatumomab, by rituximab, and by genetically engineered chimeric antigen receptor-modified T-cells. These treatments, variously targeting CD22, CD20 and CD19 antigens, yield unprecedented high rates of hematologic and molecular remissions even when used in monotherapy and in chemo-resistant or post-transplantation relapsed patients. Beside the encouraging results in relapsed/refractory disease, these agents may open a totally new era in the frontline management of this illness, redefining treatment standards and options for different risk subsets and placing the achievement of a molecular remission at the forefront of treatment objectives. The ever increasing importance of modern immunotherapy in improving treatment design and therapeutic outcome is reviewed.
[Acute lymphoblastic leukemia with Philadelphia chromosome: treatment with kinase inhibitors]. [2022]Distinct clinicopathologic acute lymphoblastic leukemia (ALL) entities have been identified, resulting in the adoption of risk-oriented treatment approaches. In Philadelphia chromosome-positive ALL, the optimal treatment requires the addition of BCR-ABL tyrosine kinase inhibitors, as imatinib. Despite advances, the outcome remains poor, and novel agents are desperately required. The emergence of resistance to the Bcr-Abl inhibitor imatinib mesylate in patients with Philadelphia chromosome-positive (Ph+) ALL has prompted the development of second-generation compounds active against mutant forms, including dasatinib and nilotinib.
The ABCs of Immunotherapy for Adult Patients With B-Cell Acute Lymphoblastic Leukemia. [2019]To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL).
Management of adverse effects of new monoclonal antibody treatments in acute lymphoblastic leukemia. [2020]Therapeutic options for relapsed/refractory B-cell acute lymphoblastic leukemia have evolved in the past few years. The FDA has approved three novel therapies for this disease: inotuzumab ozogamicin (an anti-CD22 antibody-drug conjugate), blinatumomab (a bispecific T-cell engager), and chimeric antigen receptor T-cell therapy. Although these novel immunotherapies have revolutionized the therapeutic landscape, it is important to understand the crucial aspects of administration, especially toxicity. In this article, we review the unique toxicities and adverse effects of blinatumomab and inotuzumab ozogamicin and provide recommendations for prevention of adverse effects as well as the management options for each medication.
Approval of brexucabtagene autoleucel for adults with relapsed and refractory acute lymphocytic leukemia. [2022]In October 2021, brexucabtagene autoleucel became the first anti-CD19 chimeric antigen receptor T-cell product to receive approval from the Food and Drug Administration to treat adults with relapsed and refractory B-cell acute lymphoblastic leukemia. The approval is based on results from the Zuma-3 trial and significantly widens treatment options for this patient population. In this article, we review outcomes from this study and its implications.
Safety of Anticancer Agents Used in Children: A Focus on Their Off-Label Use Through Data From the Spontaneous Reporting System. [2022]Among factors influencing the higher risk of developing unknown or rare adverse drug reactions (ADRs) among children and adolescents, there is the frequent off-label use of drugs that seems to be very common in pediatric oncological patients. Our study aim to collect and evaluate data on the safety profile of antineoplastic drugs and their off-label use in the pediatrics population using real life data.
Targeted therapy paves the way for the cure of acute lymphoblastic leukaemia. [2020]The past decade has witnessed tremendous progress in the treatment of acute lymphoblastic leukaemia (ALL), primarily due to the development of targeted therapies, including tyrosine kinase inhibitors targeting BCR-ABL1 tyrosine kinase, monoclonal antibodies targeting cell surface antigens (CD19, CD20 and CD22), bispecific antibodies and chimeric antigen receptor T- cell therapy. A number of new therapies have been approved by the US Food and Drug Administration in the past 5 years, including blinatumomab in 2014, inotuzumab ozagamicin in 2017 and tisagenlecleucel in 2017 for relapsed/refractory ALL. This has led to tremendous improvement in long-term survival, of more than 50% in patients with precursor B-ALL [50-70% in patients with Philadelphia chromosome (Ph)-positive ALL)], 50-60% in T-ALL and 80% in mature B-ALL. Research is ongoing to optimize the benefit of targeted therapeutics with the goal of decreasing the use of cytotoxic therapies.
Treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia. [2019]The use of imatinib, as part of front-line treatment and in combination with cytotoxic agents, has greatly improved the proportions of complete response and molecular remission, and overall outcome in adults with newly diagnosed Philadelphia chromosome acute lymphoblastic leukemia. New challenges have emerged with respect to induction of resistance to imatinib via ABL mutations. Several novel kinase inhibitors with significantly more potent anti-leukemic activity than imatinib are currently being developed.