Cell Therapy for High Risk T-Cell Malignancies Using CD7-Specific CAR Expressed On Autologous T Cells
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|ClinicalTrials.gov Identifier: NCT03690011|
Recruitment Status : Not yet recruiting
First Posted : October 1, 2018
Last Update Posted : April 15, 2020
Patients eligible for this study have a type of blood cancer called T-cell leukemia or lymphoma (lymph gland cancer).
The body has different ways of fighting infection and disease. This study combines two different ways of fighting disease with antibodies and T cells. Antibodies are types of proteins that protect the body from bacterial and other diseases. T cells, or T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and T cells have been used to treat cancer; they have shown promise, but have not been strong enough to cure most patients.
T cells can kill tumor cells but there normally are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person.
The antibody used in this study is called anti-CD7. This antibody sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD7. CD7 antibodies have been used to treat people with T-cell leukemia and lymphoma. For this study, anti-CD7 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor.
In the laboratory, investigators have also found that T cells work better if they also add proteins that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells grow better and last longer in the body, thus giving the cells a better chance of killing the leukemia or lymphoma cells. Finally, to make sure the T cells are able to grow and expand properly without accidentally targeting themselves (because they also have CD7 on their surface), investigators have removed the CD7 gene in the T cells using a genome editing technique called CRISPR-Cas9. Investigators have repeatedly shown in the laboratory and in our animal studies that removing the CD7 genes in T cells using CRISPR-Cas9 before adding the CAR to the cells helps them expand and kill better, and does not interfere with the other functions of the T cells.
In this study, investigators attach the CD7 chimeric receptor with CD28 added to it to T cells that have had CD7 removed from their surface. Investigators will then test how long the cells last. These CD7 chimeric receptor T cells with CD28 are investigational products not approved by the Food and Drug Administration.
|Condition or disease||Intervention/treatment||Phase|
|T-cell Acute Lymphoblastic Leukemia T-cell Acute Lymphoblastic Lymphoma T-non-Hodgkin Lymphoma||Genetic: CD7.CAR/28zeta CAR T cells Drug: Fludarabine Drug: Cytoxan||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Cell Therapy for High Risk T-Cell Malignancies Using CD7-specific CAR Expressed On Autologous T Cells (CRIMSON)|
|Estimated Study Start Date :||March 1, 2021|
|Estimated Primary Completion Date :||May 1, 2023|
|Estimated Study Completion Date :||May 1, 2038|
Experimental: CD7.CAR/28zeta CAR T Cells
Three dose levels will be evaluated. The T cells will be administered with Cytoxan and fludarabine.
Genetic: CD7.CAR/28zeta CAR T cells
Three dose levels will be evaluated: Dose level one: 1×10^7 cells/m^2, Dose level two: 3×10^7 cells/m^2, Dose level three: 1×10^8 cells/m^2
Patients will receive 3 daily doses of fludarabine (30 mg/m^2) to induce lymphopenia, finishing at least 24 hours before T cell infusion. Infusions should be given following hospital/pharmacy recommendations (including dose adjustments as appropriate per institutional guidelines) however at a minimum the fludarabine should be infused over 30 minutes. Mesna, IV hydration and anti-emetics should also be provided following local institutional guidelines.
Other Name: Fludara
Patients will receive 3 daily doses of cyclophosphamide (500 mg/m^2/day) to induce lymphopenia, finishing at least 24 hours before T cell infusion. Infusions should be given following hospital/pharmacy recommendations (including dose adjustments as appropriate per institutional guidelines); however at a minimum, the cyclophosphamide should be infused over 1 hour. Mesna, IV hydration and anti-emetics should also be provided following local institutional guidelines.
Other Name: cyclophosphamide
- Number of patients with dose limiting toxicity [ Time Frame: 6 weeks ]To evaluate the safety of escalating doses of autologous peripheral blood T lymphocytes (ATLs) genetically modified to express chimeric antigen receptors (CAR) targeting the CD7 molecule (CD7.CAR) in combination with lymphodepletion in patients with relapsed/refractory T-cell malignancies.
- Overall Response Rate [ Time Frame: 6 weeks ]To measure the anti-tumor effects of CD7.CAR-ATLs in patients with T-cell leukemia or lymphoma.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03690011
|Contact: LaQuisa Hill, MD||713-441-1450||LaQuisa.Hill@bcm.edu|
|Contact: Rayne Rouce, MDfirstname.lastname@example.org|
|United States, Texas|
|Houston Methodist Hospital|
|Houston, Texas, United States, 77030|
|Contact: LaQuisa HIll, MD 832-824-4670 LaQuisa.Hill@bcm.edu|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Contact: Rayne Rouce, MD 832-824-4716 email@example.com|
|Principal Investigator:||Rayne Rouce, MD||Pediatrics, Baylor College of Medicine|
|Principal Investigator:||LaQuisa Hill, MD||Baylor College of Medicine|
|Principal Investigator:||Maksim Mamonkin, PhD||Baylor College of Medicine|
|Principal Investigator:||Malcolm K Brenner, MB, PhD||Baylor College of Medicine|