RightFit
RecruitingPhase 1

Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)

Phase I Study of Activated T-Cells Expressing Second or Third Generation CD19-Specific Chimeric Antigen Receptors for Advanced B-Cell Non-Hodgkin's Lymphoma, Acute Lymphocytic Leukemia and Chronic Lymphocytic Leukemia (SAGAN)

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
Up to 75 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Infusions, Injections

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "This drug will decrease the numbers of the subject's own T cells before infusion of the CD19 chimeric receptor T cells."
  • "Patients will be given an injection of cells into the vein through an IV at the assigned dose."
  • "The injection will take about 20 minutes."
  • "The investigators will follow them in the clinic after the injection for up to 3 hours."
  • "The first repeat infusion can only take place at least 6 weeks after the first infusion."
  • "Any additional infusions after that would be at least 4 weeks apart."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests two types of lab-changed T cells, immune cells that target a marker called CD19 on cancer cells. It is for people age 75 or younger with certain B-cell lymphomas or leukemias that came back, did not respond to treatment, or cannot be treated with standard care. Researchers want to find the highest safe dose, learn about side effects, and see how long the cells last and whether they help fight cancer.

Subjects on this study have a type of lymph gland cancer called Non-Hodgkin Lymphoma, acute lymphocytic leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as "lymphoma" or "leukemia"). The lymphoma or leukemia has come back or has not gone away after treatment. The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Both antibodies and T cells have been used to treat patients with cancer. They have shown promise, but have not been strong enough to cure most patients. T cells can kill tumor cells but normally there 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-CD19. It first came from mice that have developed immunity to human lymphoma. This antibody sticks to lymphoma cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, anti-CD19 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, the investigators 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 last longer in the body but not long enough for them to be able to kill the lymphoma cells. The investigators believe that if they add an extra stimulating protein, called CD137, the cells will have a better chance of killing the lymphoma cells. The investigators are going to see if this is true by putting the CD19 chimeric receptor with CD28 alone into half of the cells and the CD19 chimeric receptor with CD28 and CD137 into the other half of the cells. These CD19 chimeric receptor T cells with CD28 and with or without CD137 are investigational products not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to see how long the T cell with each sort of chimeric receptor lasts, to learn what the side effects are and to see whether this therapy might help people with lymphoma or leukemia.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have B-cell lymphoma, acute lymphocytic leukemia (ALL), or chronic lymphocytic leukemia (CLL) that came back, or be newly diagnosed and unable to receive or finish standard treatment. Certain people with aggressive lymphoma planning high-dose treatment and a transplant of their own stem cells may also qualify.
  • Cancer cells must have the CD19 marker before study treatment.
  • Be age 75 or younger. The first 3 people treated must be at least 18.
  • Meet blood count, liver, kidney, and blood-clotting test rules for blood collection and treatment. Blood oxygen must be above 90% without extra oxygen.
  • Meet the study’s daily activity score and be expected to live more than 12 weeks.
  • Have recovered from short-term chemotherapy side effects at least one week before joining. Both required types of lab-changed T cells must be available and meet study standards.
  • If sexually active, agree to use effective birth control during the study and for 6 months afterward. The male partner should use a condom.
  • The patient or legal guardian must understand and sign a consent form. A donor must also consent when needed.

Who can't join

  • At blood collection: have an active infection that needs antibiotics.
  • At blood collection: have a history of another cancer, unless it was treated successfully with the aim of curing it at least 2 years earlier. Some skin cancers and early breast or cervix cancers that have not spread are exceptions.
  • At treatment: be receiving another experimental treatment or have received a cancer vaccine in the past 6 weeks. PD1/PDL1 drugs, which help the immune system fight cancer, are allowed.
  • Have had an allergic reaction to products containing mouse proteins.
  • Be pregnant or breastfeeding.
  • Have a tumor that could block breathing if it grows larger.
  • Have an active infection with HIV or HTLV.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: PROCUREMENT Referred patients (or respective donors) will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include: * Diagnosis of recurrent B-cell lymphoma or leukemia (ALL or CLL), or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory aggressive B-cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation. * CD19-positive tumor (result can be pending at this time). * Age \<= 75 years. The first 3 patients treated on the study should be adults (\>= 18 years). * Hgb greater than or equal to 7.0 (can be a transfused value) * If pheresis required to collect blood: * Creatinine \< 1.5 x upper limit normal * AST \<1.5 × upper limit normal * PT and APTT \<1.5 × upper limit normal * Informed consent explained to, understood by and signed by patient/guardian (and donor, where applicable). Patient/guardian given copy of informed consent. TREATMENT * Diagnosis of recurrent B-cell lymphoma leukemia (ALL or CLL), or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory aggressive B-cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation. * CD19-positive tumor. * Age \<= 75 years. The first 3 patients treated on the study should be adults (\>= 18 years). * Bilirubin less than 3 times the upper limit of normal. * AST less than 5 times the upper limit of normal. * Estimated GFR \> 50 mL/min * Pulse oximetry of \> 90% on room air * Karnofsky or Lansky score of \> 60%. * Recovered from acute toxic effects of prior chemotherapy at least one week before entering this study. PD1/PDL1 inhibitors will be allowed if medically indicated. * Available autologous or syngeneic activated peripheral blood T cell products (CD28ζ and CD28/CD137ζ) with more than or equal to 15% expression of CD19.CAR determined by flow cytometry. * Life expectancy of greater than 12 weeks. * 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. * Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form. Exclusion Criteria: PROCUREMENT * Active infection requiring antibiotics. * No 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 * Currently receiving any investigational agents or received any tumor vaccines within the previous 6 weeks. (Note treatment with PD1/PDL1 inhibitors is allowed.) * History of hypersensitivity reactions to murine protein-containing products. * Pregnant or lactating. * Tumor in a location where enlargement could cause airway obstruction. * Active infection with HIV or HTLV.

Study sites (2)

TX