Cell therapy using engineered T cells for high-risk T-cell cancers

Cell Therapy for High Risk T-cell Malignancies Using CD7-Specific CAR Expressed on Non-Edited T Cells (CRIMSON-NE)

This study is testing a new treatment for patients with high-risk T-cell cancers by using their own modified T cells to better target and kill cancer cells.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: N/A to 75 Years
• Sex: All
• Sponsor: Baylor College of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine
• Locations: 2 sites (Houston, Texas and 1 other locations)
• Trial ID: NCT03690011 on ClinicalTrials.gov

What this trial studies

This clinical trial focuses on patients with high-risk T-cell malignancies, specifically T-cell acute lymphoblastic leukemia and lymphoma. It employs a novel approach by using autologous T cells that are genetically modified to express a CD7-specific chimeric antigen receptor (CAR) to enhance their ability to target and kill cancer cells. Patients will undergo a process where their T cells are extracted, modified using a retrovirus to include the CD7 antibody gene, and then expanded in the lab before being reinfused. The study also incorporates chemotherapy to create an optimal environment for the modified T cells to proliferate and function effectively.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals diagnosed with recurrent or refractory T-cell acute lymphoblastic leukemia or lymphoma who are suitable for allogeneic hematopoietic stem cell transplant.

Not a fit: Patients with T-cell malignancies that are not recurrent or refractory, or those who are not suitable for stem cell transplant, may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with high-risk T-cell malignancies that are resistant to standard therapies.

How similar studies have performed: Other studies utilizing CAR T-cell therapy have shown promising results in treating various hematological malignancies, indicating a potential for success with this novel approach.

Eligibility criteria

Procurement Inclusion Criteria:

Referred patients will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include:

1\. Diagnosis of recurrent or refractory T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher) or other cutaneous T-cell lymphomas

AND

1. suitable for allogeneic hematopoietic stem cell transplant (HSCT)
2. with a suitable donor identified by a FACT accredited transplant center
3. willing to proceed to transplant if the CD7.CAR treatment induces complete remission and the patient/donor remain suitable candidates

Using NMDP donor assessment criteria, suitability is defined as "during the search process, a donor is medically fit to proceed to the next step- whether high-resolution or confirmatory HLA testing OR donor work-up." Documentation of suitability (including above criteria) will be confirmed by the investigator prior to treatment.

* For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated.

  2\. CD7-positive tumor (≥20% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory).

  3\. Age \</=75 years old.. NOTE: The first three (3) patients treated on the study must be adults (\>/=18 yrs of age).

  4\. Hgb ≥ 7.0 (can be transfused)

  5\. Life expectancy greater than 12 weeks

  6\. If pheresis required to collect blood:
  * Cr \< 1.5 upper limit normal
  * AST \< 5 × upper limit normal
  * PT and APTT \<1.5 × upper limit normal

    7\. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

Procurement Exclusion Criteria:

1. Active infection requiring antibiotics.
2. Active infection with HIV
3. History of other cancer (except non-melanoma skin cancer or in situ breast cancer or cervix cancer) unless the tumor was successfully treated with curative intent at least 2 years before trial entry.

Treatment Inclusion Criteria:

1\. Diagnosis of recurrent or refractory T-cell acute lymphoblastic leukemia (T-ALL),T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher) or other cutaneous T-cell lymphomas

AND

1\) suitable for allogeneic hematopoietic stem cell transplant (HSCT) 2) with a suitable donor identified by a FACT accredited transplant center 3) willing to proceed to transplant if the CD7.CAR treatment induces complete remission and the patient/donor remain suitable candidates

Using NMDP donor assessment criteria, suitability is defined as "during the search process, a donor is medically fit to proceed to the next step- whether high-resolution or confirmatory HLA testing OR donor work-up." Documentation of suitability (including above criteria) will be confirmed by the investigator prior to treatment.

* For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated.

  2\. CD7-positive tumor (≥20% CD7+ blasts by flow cytometry or immunohistochemistry (tissue) assessed in a CLIA certified Flow Cytometry/Pathology laboratory.

  3\. Age \</=75 years old. NOTE: The first three (3) patients treated on the study must be adults (\>/=18 yrs of age).

  4\. Bilirubin less than 3 times the upper limit of normal.

  5\. AST less than 5 times the upper limit of normal.

  6\. Estimated GFR ≥ 50 mL/min.

  7\. Pulse oximetry of \> 90% on room air

  8\. Karnofsky or Lansky score of ≥ 60.

  9\. Recovered from acute toxic effects of prior chemotherapy at least one week before entering this study.

  10\. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.

  11\. Informed consent explained to, understood by, and signed by patient/guardian. Patient/guardian given copy of informed consent.

Treatment Exclusion Criteria:

1. Currently receiving any investigational agents or having received any tumor vaccines within the previous 6 weeks.
2. History of hypersensitivity reactions to murine protein-containing products.
3. Pregnant or lactating.
4. Tumor in a location where enlargement could cause airway obstruction (per investigator discretion).
5. Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6.
6. Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF≤30% or LVEF≤50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment).
7. CNS abnormalities: Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 WBCs per mm3 (unless negative by the Steinherz/Bleyer algorithm); Presence of any CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage within the past 12 months, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.

Where this trial is running

Houston, Texas and 1 other locations

• Houston Methodist Hospital — Houston, Texas, United States (Recruiting)
• Texas Children's Hospital — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Rayne Rouce, MD — Pediatrics, Baylor College of Medicine
• Study coordinator: LaQuisa Hill, MD

Conditions T-cell Acute Lymphoblastic Lymphoma; T-non-Hodgkin Lymphoma; T-cell Acute Lymphoblastic Leukemia; Autologous CAR T cells; T-cell acute lymphoblastic lymphoma; T-non-Hodgkin lymphoma