A Phase I/II study to evaluate AUTO3 in children and adults with acute lymphoblastic leukaemia who have previously received approved treatment(s).
- Conditions
- Acute lymphoblastic leukaemia (ALL)MedDRA version: 20.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004680-39-GB
- Lead Sponsor
- Autolus Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 70
Paediatric and young adult patients
1. Male or female paediatric and young adults (age 1-24 years) with high risk relapsed or refractory B-cell Acute Lymphoblastic Leukaemia
2. Documented CD19 and or CD22 expression
3. Detectable disease in the bone marrow (Phase I) at enrolment
4. Absolute Lymphocyte Count =0.5 x 10e9/l at enrolment
5. Adequate renal, hepatic, pulmonary & cardiac function including:
- Left ventricular shortening fraction =28% confirmed by ECHO, or left ventricular ejection fraction (LVEF) =45% confirmed by ECHO.
- Baseline oxygen saturation >92% on room air.
6. Karnofsky (age 10-24 years) or Lansky (age < 10 years) score = 50%
7. Willing and able to give written informed consent/assent.
Phase II Only:
8. Primary refractory disease defined as MRD >5% blasts in the BM by flow cytometry or molecular assay following frontline induction therapy OR
- Patients with Philadelphia chromosome-positive ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated OR
- Isolated CNS relapse but with =CNS grade 2 disease at time of enrolment
Adult patients
1. Age 25 or older
2. Eastern cooperative oncology group performance status of 0 or 1
3. Relapsed or refractory B-precursor ALL defined as one of the following:
4. Patients with Philadelphia chromosome positive ALL are eligible if they are intolerant to or have failed 2 lines of TKI therapy, or if TKI therapy is contraindicated
5. Documentation of CD19 and/ or CD22 expression on leukaemic blasts in the BM, peripheral blood, or CSF by flow cytometry within 3 months of screening
6. For females of childbearing potential, a negative serum or urine pregnancy test
7. For females who are not postmenopausal or who are not surgically sterile & males, two methods of contraception should be used
8. Absolute lymphocyte count =0.5 x 109/L at enrolment
9. Adequate renal, hepatic, pulmonary, and cardiac function defined as:
- LVEF =45% confirmed by ECHO or MUGA.
- Baseline oxygen saturation >92% on room air
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
Paediatric and young adult patients
1. Isolated extramedullary disease relapse (in Phase II, patients with isolated CNS relapse post-SCT or pre-SCT if high risk, aged 16-24 years on therapy relapse or = 2nd relapse with =CNS grade 2 disease at time of enrolment)
2. Active CNS involvement of ALL, defined by CNS Grade 3 per National Comprehensive Cancer Network guidelines. Patients developing CNS Grade 3 disease at any time after enrolment will also be excluded
3. Active infectious bacterial or viral disease requiring treatment.
4. Females who are pregnant or lactating.
5. Females of child-bearing potential and post-pubertal males who unwilling to use highly effective methods of contraception during the treatment period and 1 year after AUTO3 infusion.
6. Pre-existing significant neurological disorder
7. Stem Cell Transplant patients only: active significant (overall Grade =II, Seattle criteria) acute graft versus host disease (GVHD) or moderate/severe chronic GVHD (National Institutes of Health [NIH] consensus criteria) requiring systemic steroids or other immunosuppressant within 4 weeks of enrolment
8. The following treatments are excluded:
- Steroids: Therapeutic doses must be stopped >72 hours prior to AUTO3 infusion and leukapheresis.
- Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed >6 weeks prior to AUTO3 infusion
- GVHD therapies: Any drug used for GVHD must be stopped >4 weeks prior to AUTO3 infusion
- Chemotherapy: Stopped 1 week prior to leukapheresis and 2 days prior to starting pre-conditioning chemotherapy
- Intrathecal therapy: Methotrexate within 4 weeks and other intrathecal chemotherapy (eg Ara-C) within 2 weeks prior to starting pre conditioning chemotherapy.
- Live vaccine = 4 weeks prior to enrolment.
9. Known allergy to albumin, dimethyl sulfoxide, cyclophosphamide or fludarabine.
Adult patients
1. Isolated extramedullary disease
2. Diagnosis of Burkitt's leukaemia/lymphoma or chronic myelogenous leukaemia lymphoid blast crisis
3. Females who are pregnant or lactating
4. History or presence of clinically relevant CNS pathology within 3 months prior to enrolment, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis
5. Presence of CNS-3 disease or CNS-2 disease with neurological changes. Patients developing CNS Grade 3 disease or symptomatic CNS-2 disease at any time after enrolment will also be excluded
6. Clinically significant, uncontrolled heart disease or a recent cardiac event
7. Patients with a history or evidence of pulmonary embolism requiring ongoing therapeutic anticoagulation at the time of pre-conditioning
8. Patients with active gastrointestinal bleeding
9. Patients with any major surgical intervention in the last 3 months
10. Active infectious bacterial or viral disease or fungal requiring treatment with i.v. antimicrobials
11. History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months. Any autoimmune disease with CNS involvement
12. History of other malignant neoplasms unless disease free for at least 24 months
13. History of concomitant genetic syndrome such as Fanconi anaemia, Shwachman-Diamond syndrome, Kostmann syndrome or any other known BM failure syndrome
14. Stem cell transplant patients only: Active significant acute GVHD or moderate/severe chronic GVHD) requiring systemic s
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method