Acute Lymphoblastic Leukemia, Pediatric, Refractory Acute Lymphoblastic Leukemia, Relapsed Acute Lymphoblastic Leukemia
Conditions
Keywords
ALL, Relapsed ALL
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
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).
Interventions
DRUGPalbociclib
Oral
DRUGDexamethasone
8 mg/m2/day divided BID, PO, NG, or IV
DRUGBortezomib
1.3 mg/m2/dose, IV (preferred) or SC
DRUGDoxorubicin
25 mg/m2/dose IV
Sponsors
Tanja Andrea Gruber
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Participants must have a diagnosis of acute lymphoblastic leukemia and disease meets at least one of the following criteria: 1. 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 2. relapsed after hematopoietic stem cell transplantation (HSCT) 3. Subjects must have had histologic, morphologic or flow cytometric verification of the malignancy at relapse 2. Prior Treatment: 1. Subjects who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study. 2. 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. 3. At least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of standard maintenance therapy and steroids. 4. 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. 5. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting Toxicity (DLT) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 24 months | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTanja A Gruber, MD
Stanford Universiy
Outcome results
None listed