None listed
Conditions
Brief summary
Patients with relapsed ALL will receive 18 days of oral Everolimus (RAD001) in combination with HyperCVAD therapy. The first 6 patients will receive 2.5mg dose of RAD001. The data of these 6 will be reviewed to assess whether or not subsequent patients can progress to 5mg dose of RAD001, or the trial should be closed.
Interventions
Patients suffering from ALL in first or subsequent relapse will start oral RAD001 (everolimus) treatment (either 2.5mg or 5mg depending on which study cohort is open) once daily on day 1 for a total of 18 doses in 18 days in conjunction with the HyperCVAD regimen. Patients achieving complete remission by day 21 of the preceding chemotherapy cycle can proceed with subsequent cycles of the same RAD001 dose and HyperCVAD up to a total of 4 cycles.
The first cohort of 6 patients will receive 2.5mg
Patients suffering from ALL in first or subsequent relapse will start oral RAD001 (everolimus) treatment (either 2.5mg or 5mg depending on which study cohort is open) once daily on day 1 for a total of 18 doses in 18 days in conjunction with the HyperCVAD regimen. Patients achieving complete remission by day 21 of the preceding chemotherapy cycle can proceed with subsequent cycles of the same RAD001 dose and HyperCVAD up to a total of 4 cycles. The first cohort of 6 patients will receive 2.5mg dose of RAD001. The data of each cohort will be reviewed to assess whether or not subsequent cohorts of patients can be given 2.5mg or 5mg dose of RAD001 or whether the trial should be closed.
Sponsors
Australasian Leukaemia and Lymphoma Group
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Morphologically and immunophenotypically confirmed diagnosis of precursor B ALL, negative for Philadelphia chromosome/ bcr-abl fusion transcripts, in first or subsequent relapse more than 6 months after starting treatment with a standard combination chemotherapy protocol. Has provided written informed consent Must be surgically sterile or female and postmenopausal (ie >12 mths since the last menstrual cycle) or, if capable of parenting a child, must be using medically acceptable and adequate method of contraception while undergoing protocol treatment and until 90 days after the last treatment. Adequate renal, hepatic and cardiac functions at Screening as defined by: Serum bilirubin <2.5 x upper limit of normal (ULN) Serum creatinine < 1.5ULN, unless medically correctable Adequate cardiac function with left ventricular ejection fraction (LVEF) >40% and no major left ventricular dysfunction An Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less at Screening
Exclusion criteria
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.
Outcome results
None listed