REALIB-LLA-2017: Idelalisib in Patients With Acute Lymphoblastic Leukemia

• Status: Terminated
• Trial end date: 2020-06-02
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PETHEMA Foundation
• Treatments: Idelalisib

Criteria

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 2.

• 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.

• Women of childbearing potential: must agree to practice abstinence (abstain from having heterosexual sexual relations/contact) or to use one highly effective birth control method (failure rate less than 1%) during the treatment period and for at least 28 day after the last dose of Idelalisib .

• A woman is considered able to conceive if she is menstruating, is not post-menopausal (≥12 consecutive months without menstruation for no cause other than menopause) and who has not undergone surgical sterilization (removal of ovaries or uterus).

• Examples of birth control methods with a <1% yearly failure rate include bilateral tubal ligation, vasectomy, proper use of hormonal contraceptives that prevent ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

• The feasibility of sexual abstinence should be evaluated with respect to the duration of the trial and the patient's normal lifestyle preferences. Periodic abstinence (for example, the calendar method, ovulation, symptothermal or post-ovulation methods) and the withdrawal method are not acceptable birth control methods.

• Male patients: must agree to practice abstinence (abstain from heterosexual sexual relations) or use birth control methods, and agree to not donate sperm, as defined below:

• With female partners of childbearing capacity or pregnant female partner, men must practice total abstinence or use a condom plus one additional birth control method which, combined, have a failure rate of <1% per year during the treatment period, and for at least 4 months after the last dose of Idelalisib to avoid exposure to the fetus. Men must not donate sperm during this same time period.

• The feasibility of sexual abstinence should be evaluated with respect to the duration of the trial and the patient's lifestyle preferences. Periodic abstinence and the withdrawal method are not acceptable birth control methods.

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.

• Patients with active chronic hepatitis, including viral hepatitis.

• Patients with HIV.

• Medical history of pneumonitis or any baseline lung disorder that, in the investigator's opinion, might worsen the patient's prognosis in the event of opportunistic pneumonia