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.
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
Drug | Synonyms | Arms |
---|
CLIC-1901 | autologous anti-CD19 CAR-T cells | CLIC-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
Name | Type | Description | Interventions |
---|
CLIC-1901 | Experimental | A single Intravenous infusion of CLIC-1901 will be given. | |
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
Last Updated
February 24, 2021