Phase I-II Unmasked, Non-randomized Study Evaluating the Role of Idelalisib in Patients With Acute Lymphoblastic Leukemia (ALL) That is Relapsing or Refractory to Other Treatments, and in Older Patients With ALL for Whom Conventional Treatments Are Not Recommended
Overview
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- PETHEMA Foundation
- Enrollment
- 6
- Locations
- 12
- Primary Endpoint
- Response duration
Overview
Brief Summary
This study will attempt to confirm the hypothesis that Idelalisib may represent a new therapeutic alternative for patients with ALL in a set of particularly complex scenarios: relapsed, refractory to conventional treatments, and old age. For this reason, the primary objective is the overall response rate [ORR, defined as complete response (CR) or CR with partial hematologic recovery (CRh) and response duration (RD) in adult patients with relapsed or refractory ALL, or in adult ALL patients who are not suitable for treatment with conventional therapies.
Detailed Description
Phase I-II multi-site, exploratory, interventional, unmasked, non-randomized, single arm clinical trial. A single drug will be administered in four different, increasing doses to four consecutive cohorts.
The first phase of the study will focus on determining the most effective and tolerated dose of the study drug. The second phase will follow patients to the end to evaluate the safety of the drug.
The dose escalation will be decided by the Study Coordinator, who will evaluate and assess each cohort. Once the cohort of 6 patients is complete, the Coordinator will evaluate patients and, based on the tolerability and efficacy obtained, will decide whether to proceed with the dose escalation, or whether to end the trial The study will remain open until the overall number of participants is achieved; §progressive dose increases (PI) will be discontinued if dose-limiting toxicity (DLT) is observed in more than two patients in the previous cohort, *PI of the dose will only continue (for the third cohort) if at least two patients in the first two cohorts achieve the overall response rate (ORR), that is, complete response (CR) at four weeks from initiation of treatment; ** the study will only move on to the fourth cohort if CR is achieved in at least one of the six patients in the third cohort at four weeks from initiation of treatment; ***microscopy/cytofluorometry; ****complete blood count, microscopy, biochemistry; *****as long as there is no relapse, treatment will continue after the end of the study (planned for 24 months after the start of recruitment); AE, adverse events
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥18 years.
- •B-cell precursor ALL, in any of the following cases:
- •Second or subsequent relapses \[including after hematopoeitic stem cell transplantation (HSCT)\] in patients who are ineligible for subsequent HSCT.
- •Resistance to at least two lines of treatment. Line of treatment is understood as initial treatment y salvage therapy after the first relapse (that may include HSCT).
- •Older adult patients (aged \>65 years) for whom standard therapies are not clinically advisable.
- •In patients with Ph+ ALL, failure after receiving at least two treatments with different TKIs (tyrosine kinase inhibitors): imatinib, dasatinib or ponatinib, in patients who are ineligible for subsequent HSCT.
- •ECOG between 0 and
- •Aspartate transaminase (AST) and alanine aminotransferase (ALT) values \< two times the upper limit of normal (ULN) and total bilirubin 2 mg/dL.
- •Creatinine \<2 mg/dL
- •More than 10% blasts in bone marrow in the two weeks prior to the start of the trial.
Exclusion Criteria
- •Isolated central nervous system relapse.
- •Patients planning to undergo HSCT.
- •Any active systemic fungal, bacterial, or viral infection at the time of inclusion in the study.
- •Grade II-IV active diarrhea.
- •Grade II-IV active liver toxicity.
- •Previous treatment with other PI3K/mTOR inhibitors.
- •Taking any other experimental drug at the time of entering the trial. Patients who have completed a 4-week washout period will be permitted to enrol in the trial.
- •Taking any antineoplastic drugs at the time of entering the trial (an exception is made for patients being treated with hydroxyurea or glucocorticoids. Use of these drugs is allowed up to 24 hours before initiating treatment with Idelalisib ).
- •Patients being treated with moderate or potent CYP3A4 inhibitors or inducers.
- •Patients with Stevens-Johnson Syndrome and toxic epidermal necrolysis.
Arms & Interventions
Idelalisib
Intervention: Idelalisib (Drug)
Outcomes
Primary Outcomes
Response duration
Time Frame: 6 months
Time to response duration
Overall Response Rate
Time Frame: 6 months
overall response rate (ORR), defined as CR (blasts in bone marrow aspiration \<5%; neutrophils \>1x109/L and platelets\>100x109/L in peripheral blood) or CR with partial hematologic recovery (RCh) (blasts in bone marrow aspiration \<5%; neutrophils\<1x109/L and/or platelets \<100x109/L in peripheral blood).
Secondary Outcomes
- Determine overall survival (OS).(24 months)
- Determine progression free survival (PFS).(6 months)
- Overall Response Rate in subgroups(6 months)
- Percentage of Adverse Events(6 months)