AUTO1 in Relapsed or Refractory B-ALL

Overview

About this study

The purpose of this study is to evaluate the safety and effectiveness of AUTO1 (t-cells) in adult patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukaemia (r/r B-ALL).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age 18 years or older.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Relapsed or refractory B cell ALL defined as one of the following:
    • Primary refractory disease (not achieving CR after two cycles of induction chemotherapy);
    • First relapse if first remission ≤ 12 months (Phase Ib Cohort IA and Phase II Cohort IIA);
    • Relapsed or refractory disease after two or more lines of systemic therapy;
    • Relapsed or refractory disease after allogeneic transplant provided AUTO1 infusion occurs at least 3 months after stem cell transplant.
  • Patients with Philadelphia chromosome positive ALL (Ph+ ALL) are eligible if they are intolerant to or have failed two lines of any tyrosine kinase inhibitor (TKI) or one line of second-generation TKI, or if TKI therapy is contraindicated.
  • Documentation of CD19 expression on leukaemic blasts in the BM, peripheral blood, or cerebrospinal fluid (CSF) by flow cytometry within 1 month of screening. In patients treated with blinatumomab, testing should be undertaken after blinatumomab therapy has been stopped.

Phase Ib:

  • Primary Cohort IA: Presence of ≥ 5% blasts in BM at screening.
    Exploratory Cohort IB: MRD- positive defined as ≥ 10-4 and < 5% blasts in the BM at screening.
  • Presence of ≥ 5% blasts in BM at screening.

Phase II:

  • Primary Cohort IIA: Presence of ≥5% blasts in BM at screening.
    Exploratory Cohort IIB: MRD-positive defined as ≥ 10-4 and < 5% blasts in the BM at screening or isolated EM disease with the exception of CNS disease at screening.
  • Adequate renal, hepatic, pulmonary, and cardiac function defined as:
    • Serum alanine aminotransferase/aspartate aminotransferase ≤ 2.5 x upper limit of normal (ULN);
    • Creatinine clearance (as estimated by Cockcroft Gault) ≥ 50 cc/minute;
    • Total bilirubin ≤ 1.5 x ULN, except in patients with Gilbert’s syndrome who must have normal direct bilirubin;
    • Left ventricular ejection fraction (LVEF) ≥ 45% (or ≥institutes lower limit of normal) confirmed by echocardiogram (ECHO) or multigated acquisition (MUGA) in patients with history of coronary artery disease or cardiovascular disease or those with history of low LVEF;
    • Baseline oxygen saturation > 92% on room air.

Exclusion Criteria:

  • Phase Ib (Cohort IA and Cohort IB) and Phase II Cohort IIA only: B-ALL with isolated EM disease.
  • Diagnosis of Burkitt’s leukaemia/lymphoma according to World Health Organisation (WHO) classification or chronic myelogenous leukaemia lymphoid in blast crisis.
  • History or presence of clinically relevant CNS pathology such as epilepsy, paresis, aphasia, stroke within 3 months prior to consent, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis.
  • Presence of CNS 3 disease or CNS 2 disease with neurological changes. Patients developing CNS 3 disease or symptomatic CNS 2 disease at any time after consent will also be excluded until they no longer meet these criteria.
  • Presence of active or uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management.
  • Active or latent Hepatitis B virus or active Hepatitis C virus.
  • Human Immunodeficiency Virus (HIV), human T-cell lymphotropic virus (HTLV)-1, HTLV-2, or syphilis positive test.
  • Patients who have received a prior stem cell transplant: less than 3 months prior to AUTO1 infusion. 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 immunosuppressants within 4 weeks of consent.
  • Prior CD19 targeted therapy other than blinatumomab. Patients who have experienced Grade 3 or higher neurotoxicity following blinatumomab.
  • The following medications are excluded:
    • Steroids: Therapeutic doses of corticosteroids (greater than 10 mg daily of prednisone or its equivalent) within 7 days of leukapheresis or 72 hours prior to AUTO1 administration. However, physiological replacement, topical, and inhaled steroids are permitted;
    • Immunosuppression: Immunosuppressive medication must be stopped ≥ 2 weeks prior to leukapheresis and AUTO1 infusion;
    • Allogeneic cellular therapy: any donor lymphocyte infusions must be completed > 2 weeks prior to leukapheresis and not repeated thereafter;
    • Graft versus host disease therapies: any drug used for GVHD must be stopped > 2 weeks prior to leukapheresis and not reinitiated thereafter;
    • Chemotherapy (including TKIs for Ph+ ALL): should be stopped 1 week prior to leukapheresis or starting pre-conditioning chemotherapy;
    • Treatment with any T cell lytic or toxic antibody (e.g., alemtuzumab) within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis;
    • Live vaccine ≤ 4 weeks prior to leukapheresis;
    • Intrathecal therapy within 2 weeks prior to starting pre-conditioning chemotherapy;
    • Use of blinatumomab after leukapheresis.
  • Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted.
  • Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy after starting pre-conditioning therapy on study.
  • Inability to tolerate leukapheresis
  • Patients, who in the opinion of the Investigator, may not be able to understand or comply with the safety monitoring requirements of the study or unlikely to complete all protocol-required study visits or procedures, including follow-up visits.
    • Note: Patients failing any of the eligibility criteria, after leukapheresis or AUTO1 product manufacture, such as those with progressive CNS disease and who are temporarily discontinued, may re-enter the study if they subsequently meet eligibility criteria. If AUTO1 product has been manufactured they can be treated using the original product if it continues to meet release criteria.

Eligibility last updated 8/25/21. Questions regarding updates should be directed to the study team contact.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Hassan Alkhateeb, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

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Study Results Summary

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Supplemental Study Information

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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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