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Clinical Trials/NCT03144583
NCT03144583CompletedPhase 1

Pilot Study on the Infusion of Differentiated Autologous T-cells From Peripheral Blood, Expanded and Transduced With a Lentivirus to Express a Chimeric Antigen Receptor With Anti-CD19 Specificity Conjugated With the Co-stimulatory Regions 4-1BB and CD3z in Patients With CD19+ Leukemia or Lymphoma Refractory to Therapy

Sara V. Latorre2 sites in 1 country50 target enrollmentStarted: June 15, 2017Last updated:
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Conditions
Interventions

Trial Snapshot

Phase
Phase 1
Status
Completed
Sponsor
Enrollment
50
Locations
2
Primary Endpoint
Procedure-related mortality (PRM)
Study OverviewStudy DesignEligibility CriteriaArms & InterventionsOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Study Overview

Brief Summary

To assess the infusion of ARI-0001 cells (Adult differentiated autologous T-cells from peripheral blood, expanded and transduced with a lentivirus to express a chimeric antigen receptor with anti-CD19 specificity [A3B1] conjugated with the co-stimulatory regions 4-1BB and CD3z ) safety on patients with leukemia or lymphoma CD19+ resistant or refractory to treatment and with a prognosis of less than 2 years.

Study Design

Study Type
Interventional
Allocation
Na
Intervention Model
Single Group
Primary Purpose
Other
Masking
None

Masking Description

Open label

Eligibility Criteria

Ages
2 Years to 80 Years (Child, Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • •Diagnosis of leukemia or CD19 + lymphoma, with a life expectancy less than 2 years that meet the following conditions:- Adult acute lymphoid leukemia in second or third response, not candidate for transplantation due to age, associated diseases or lack of donor, or in relapse post allogeneic transplant.- Pediatric acute lymphoid leukemia in second or third response, refractory or non-transplant candidate due to donor absence, or in relapse post allogeneic transplant, or with minimal residual residual disease (0.1% or greater) after two or more lines of treatment. - Symptomatic follicular lymphoma, which has received at least 2 treatment regimens (one of them including rituximab) and a progression-free interval of less than 2 years. Patients not candidates for transplantation or post-transplant relapse may be included.- Symptomatic chronic lymphocytic leukemia, which has received at least 2 treatment regimens (one of them including rituximab) and a progression-free survival of less than 2 years. Patients with a 17p deletion or TP53 mutation may be included after the first line of treatment. - Mantle cell lymphoma in the first relapse (or higher) when it is not a candidate for transplantation, or second post-transplant relapse (or higher). - Diffuse large cell lymphoma in first relapse (or higher) when it is not a candidate for transplantation, or second post-transplant relapse (or higher).
  • •Age greater than 2 years and less than
  • •ECOG functional status from 0 to 2
  • •Life expectancy of at least 3 months.
  • •Appropriate venous access to perform an apheresis procedure. Absence of contraindications for it.
  • •Signature of informed consent (patient or legal guardian).

Exclusion Criteria

  • •Treatment with any experimental or non-marketed substance within four weeks prior to recruitment, or actively participating in another therapeutic clinical trial.
  • •Diagnosis of another past or present neoplasm. Patients may be included in complete remission for more than 3 years, or with a history of non-melanoma skin cancer or completely resected in-situ carcinoma.
  • •Central nervous system involvement (CNS-3) at inclusion. Inclusion will be permitted with patients with a lower grade (CNS-2) or with CNS-3 who have responded to intrathecal chemotherapy.
  • •Early relapse after allogeneic transplantation (less than 3 months for apheresis of mononuclear cells, less than 6 months for infusion of ARI-0001) or patients on active immunosuppressive therapy for graft-versus-host disease (corticosteroids or other systemic immunosuppressants ).
  • •Active infection requiring systemic medical treatment such as chronic kidney infection, chronic lung infection or tuberculosis.
  • •HIV infection.
  • •Concurrent and uncontrolled medical illnesses including cardiac, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological or psychiatric diseases which in the opinion of the researcher represent a risk to the patient.
  • •Positive serology for hepatitis B, defined as a positive test for HBsAg. In addition, if the patient is HBsAg negative but has anti-HBc antibodies it will be necessary to perform a DNA test of the hepatitis B virus, and if the result is positive the patient will be excluded.
  • •Positive serology for hepatitis C, defined as a positive test for anti-HCV antibodies confirmed by RIBA.
  • •Severe organ failure, defined as a cardiac ejection fraction <40%; DLCO <40%; calculated glomerular filtrate rate <30 ml / min; Or bilirubin> 3 times the upper limit of normal (unless it is due to CLL or Gilbert syndrome).
  • •Pregnant or lactating women. Women of childbearing potential should have a negative pregnancy test in the screening phase.
  • •Women of childbearing age, including those whose last menstrual cycle was in the year prior to screening, who are unable or unwilling to use highly effective contraceptive methods from the start of the study to the end of the study.
  • •Men who are unable or unwilling to use highly effective contraceptive methods from the start of the study to the completion of the study.
  • •The need to take glucocorticoids in a chronic manner at doses higher than 10 mg / day of prednisone (or equivalent) or other chronic immunosuppressants. Hormonal contraceptives, intrauterine device, intrauterine systems of hormonal release, sexual abstinence, vasectomy of the couple or bilateral tubal occlusion.

Arms & Interventions

Adult differentiated autologous T-cells

Experimental

Adult differentiated autologous T-cells from peripheral blood, expanded and transduced with a lentivirus to express a chimeric antigen receptor with anti-CD19 specificity (A3B1) conjugated with the co-stimulatory regions 4-1BB and CD3z. Such cells will be administered in a single infusion intravenously at a total ARI-0001 cell dose of 0.5-10 x 106 / kg body weight.

Intervention: Adult differentiated autologous T-cells (Biological)

Outcomes

Primary Outcomes

Procedure-related mortality (PRM)

Time Frame: Year 3

Any death not caused directly by leukemia / lymphoma. For the estimation of PRM, relapse or progression of the disease will be considered as a competitive event.

Assessment of toxicity

Time Frame: Year 1

number of adverse events grade III-IV using CTC (common toxicity criteria)

Procedure-related mortality (PRM)

Time Frame: Year 1

Any death not caused directly by leukemia / lymphoma. For the estimation of PRM, relapse or progression of the disease will be considered as a competitive event.

Assessment of toxicity

Time Frame: Month 3

number of adverse events grade III-IV using CTC (common toxicity criteria)

Secondary Outcomes

  • In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid(months 9,12,15,18,21,24)
  • Toxicity assessment(Month 3 and year 1)
  • Response rate (overall and complete)(Month 3 and Year 1)
  • Progression-free survival(Year 2 after procedure)
  • Overall survival (OS) at 2 years(3 years)
  • Quality of life of included patients(Month 3, 6, 12)
  • In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid(months 1,2,3,4,5,6)

Investigators

Sponsor
Sara V. Latorre
Sponsor Class
Other
Responsible Party
Sponsor Investigator
Principal Investigator

Sara V. Latorre

Clinical Research Manager

Institut d'Investigacions Biomèdiques August Pi i Sunyer

Study Sites (2)

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