Clinical Trials /

CLIC-1901 for the Treatment of Patients With Relapsed/Refractory CD19 Positive Hematologic Malignancies

NCT03765177

Description:

The investigators propose an early phase study defined as a phase I/II trial assessing safety, feasibility and efficacy of CLIC-1901 autologous anti-CD19 Chimeric Antigen Receptor T cells (CAR-T) cells for participants with relapsed/refractory CD19 positive (CD19+) Acute Lymphoblastic Leukemia (ALL) and non-Hodgkin's Lymphoma (NHL). The Initial Stage of the study (n=20 participants) will focus on feasibility and safety while the Extended Stage will include all participants enrolled in the study (n=additional 40 participants for a total of 60) and will focus on efficacy and safety outcomes. In the proposed trial, we will administer our CAR-T cell product to these participants as a single infusion. Participants will undergo (a) lymphodepletion with cyclophosphamide and fludarabine, followed by (b) infusion of autologous CLIC-1901 CAR-T cells. All treatments will be delivered intravenously.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CLIC-1901 for the Treatment of Patients With Relapsed/Refractory CD19 Positive Hematologic Malignancies
  • Official Title: Canadian-Led Immunotherapies in Cancer: CLIC-1901 for the Treatment of Patients With Relapsed/Refractory CD19 Positive Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CLIC-01 Study
  • NCT ID: NCT03765177

Conditions

  • Acute Lymphoblastic Leukemia
  • Non-Hodgkin's Lymphoma

Interventions

DrugSynonymsArms
CLIC-1901autologous anti-CD19 CAR-T cellsCLIC-1901

Purpose

The investigators propose an early phase study defined as a phase I/II trial assessing safety, feasibility and efficacy of CLIC-1901 autologous anti-CD19 Chimeric Antigen Receptor T cells (CAR-T) cells for participants with relapsed/refractory CD19 positive (CD19+) Acute Lymphoblastic Leukemia (ALL) and non-Hodgkin's Lymphoma (NHL). The Initial Stage of the study (n=20 participants) will focus on feasibility and safety while the Extended Stage will include all participants enrolled in the study (n=additional 40 participants for a total of 60) and will focus on efficacy and safety outcomes. In the proposed trial, we will administer our CAR-T cell product to these participants as a single infusion. Participants will undergo (a) lymphodepletion with cyclophosphamide and fludarabine, followed by (b) infusion of autologous CLIC-1901 CAR-T cells. All treatments will be delivered intravenously.

Detailed Description

      The investigators have designed a two-stage, single-arm, open-label early phase study to
      determine the safety and efficacy of CLIC-1901 cell therapy in patients with CD19+ ALL and
      NHL. The primary objective in the initial stage of 20 participants will be to evaluate the
      feasibility of our protocol and the safety and tolerability of infusing autologous CLIC-1901
      cells into patients with relapsed/refractory CD19+ ALL or NHL. Once 20 participants have been
      treated and the treatment is deemed safe, up to 40 more participants will be enrolled in an
      extension stage where the primary objective will be overall response rate (defined as
      complete or partial response) at 6 months after CLIC-1901 infusion.
    

Trial Arms

NameTypeDescriptionInterventions
CLIC-1901ExperimentalA single Intravenous infusion of CLIC-1901 will be given.
  • CLIC-1901

Eligibility Criteria

        Inclusion Criteria:

          1. Participant must have relapsed or refractory CD19+ disease as defined by one of the
             following:

             a. Relapsed or refractory acute lymphoblastic leukemia as defined by one of the
             following: i. Second or greater relapse ii. Any relapse after allogeneic stem cell
             transplantation (SCT) iii. Chemorefractory as defined by not achieving CR after 2
             cycles of a standard induction chemotherapy or one cycle of salvage therapy b.
             Histologically confirmed B-cell non-Hodgkin's lymphoma including diffuse large B-cell
             lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma,
             or transformed follicular lymphoma with one of the following: i. Second or greater
             relapse ii. Any relapse after autologous or allogeneic SCT iii. Chemorefractory as
             defined by not achieving CR after 2 cycles of a standard chemotherapy or one cycle of
             salvage therapy

          2. All eligible participants must have documentation of CD19 tumour expression
             demonstrated in tissue biopsy, bone marrow or peripheral blood within the 3 months
             prior to study screening.

          3. Adequate organ function

          4. Participant age: 18 to 75 years.

          5. Provide written informed consent

        Exclusion Criteria:

        An individual who meets any of the following criteria will be excluded from participation
        in this study:

          1. Isolated extra-medullary disease.

          2. Participants with concomitant genetic syndrome, such as Fanconi anemia, Kostmann
             syndrome, Shwachman syndrome or any other known familial bone marrow failure syndrome.

          3. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative
             intent and with no evidence of active disease.

          4. Prior treatment with any gene therapy product.

          5. Participants with polymerase chain reaction (PCR) positive hepatitis B, hepatitis C,
             or Human Immunodeficiency Virus (tested within 8 weeks of screening), or any
             uncontrolled infection at screening.

          6. Presence of active Graft Versus Host Disease requiring systemic therapy.

          7. Participants who have undergone allogeneic SCT less than 6 months prior to CLIC-1901
             cell infusion or who have undergone donor lymphocyte infusion less than 6 weeks prior
             to CLIC-1901 cell infusion.

          8. Active Central Nervous System (CNS) involvement by malignancy, defined by CNS-3 per
             National Comprehensive Cancer Network guidelines.

          9. History of anaphylaxis to gentamicin or its derivatives.

         10. Participant has received an investigational agent within the 30 days prior to
             enrolment visit.

         11. Pregnant or nursing women.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of participants experiencing either Grade 3 or 4 cytokine release syndrome.
Time Frame:Within the first 28 days of CAR-T infusion
Safety Issue:
Description:Grade 3 or 4 neurological toxicity, other Grade 3 or 4 toxicity (by CTCAE 4.03) or non-relapse related death.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ottawa Hospital Research Institute

Trial Keywords

  • Chimeric Antigen Receptor T cells
  • CLIC-1901
  • anti-CD19 CAR-T cells

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