ALLG ALL07: This phase I trial is evaluating a new drug (Everolimus) in combination with chemotherapy for the treatment of Acute Lymphoblastic Leukaemia (ALL)Phase 1 study investigating the safety and tolerability of RAD001 (Everolimus) in combination with chemotherapy for treatment of relapsed adult acute lymphoblastic leukemia (ALL)

Exclusion

Patients with other immunophenotypic variants of ALL (precursor T, mature B)

Women who are pregnant or lactating. Women of child-bearing potential must have a negative urine pregnancy test at Screening.

Patients who have relapsed after an allogeneic transplant

Systemic chemotherapy, immunotherapy, approved proteins/antibodies or any investigational agent within 4 weeks prior to commencing study treatment

Radiotherapy within 14 days of commencing study treatment.

Prior therapy with mammalian target of rapamycin (mTOR) inhibitors (sirolimus, temsirolimus, everolimus)
Uncontrolled diabetes mellitus

CYP3A4 enzyme inducing anti-convulsant medication (eg phenytoin, phenobarbital, or carbemazepine), rifampin and rifabutin, and St. John’s Wort less than or equal to 14 days prior to study treatment

Ketoconazole less than or equal to 7 days before study treatment (Note: interaction with topical ketoconazole cannot be excluded).

Known cirrhosis, chronic active hepatitis, or chronic persistent hepatitis

Unresolved toxicities from prior systemic therapy or radiotherapy that, in the opinion of the investigator, does not qualify the patient for study treatment.

Patients with known interstitial lung disease or severely impaired lung function (spirometry and diffusional capacity lung carbon monoxide (DLCO) 50% or less of normal and oxygen saturation of 88% or less at rest on room air).

Patients who have a history of another primary malignant disease, apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse.

Any uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris
Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as common terminology criteria (CTC) grade 2)

Chronic treatment with immunosuppressives

Patients who, in the opinion of the Investigator, have any severe and/or uncontrolled medical conditions or infections that may compromise study data

Untreated or symptomatic Central Nervous System (CNS) leukaemia

Previous adverse reaction to trial drug(s)

Patients with a known history of Human Immunodeficiency Virus (HIV) seropositivity
Uncontrolled Hepatitis B or C infection. Patients positive for Hepatitis B Virus (HBV) (Hepatitis B surface antigen (HBs Ag) that is not due to vaccination, or HBV deoxyribonucleic acid (DNA)) should undergo prophylactic antiviral therapy for 2 weeks prior to the first dose of RAD001, and for 4 weeks following the last dose of RAD001.

Participation in other therapeutic studies in the last 30 days except for studies with a non-medical intervention. Documented evidence of receiving placebo will be required.

Unable to receive treatment at an affiliated Australasian Leukaemia and Lymphoma Group (ALLG) centre

Medical or psychiatric conditions that compromise the patient’s ability to give informed consent or to complete the protocol

Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.