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ANCHOR Cells for the Treatment of Patients with Relapsed or Refractory CD19-Positive B-Cell Lymphoma or Leukemia, ANCHOR Study

Trial Status: Active

This phase I clinical trial studies the best dose and side effects of allogeneic natural killer T-cells expressing CD19-specific chimeric antigen receptor and interleukin-15 (ANCHOR cells) in treating patients with CD19-positive lymphoma or leukemia that have come back (relapsed) or do not respond to treatment (refractory). This trial combines two different ways of fighting disease, antibodies, and immune cells. Antibodies are types of proteins that protect the body from bacterial and other diseases. Immune cells, also called lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and lymphocytes have been used to treat patients with cancer. The antibody used in this study is called anti-CD19. It sticks to leukemia cells because of a substance on the outside of these cells called CD19. For this clinical trial, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now joined to the NKT cells, a special type of lymphocytes that can kill tumor cells but not very effectively on their own. When an antibody is joined to a T cell in this way, it is called a chimeric receptor. In the laboratory, it has also been found that NKT cells work better if proteins that stimulate lymphocytes are added, such as one called CD28. Adding the CD28 makes the cells last for a longer time in the body but may be not long enough for them to be able to kill the leukemia cells. Adding an extra stimulating protein, called IL-15, may allow the cells an even better chance of killing the leukemia cells. This trial evaluates whether putting the anti-CD19 chimeric receptor with CD28 and the IL-15 into NKT cells grown from a healthy individual may be more effective in treating patients with relapsed or refractory CD19-positive lymphoma or leukemia.

Inclusion Criteria

  • Diagnosis of CD19-positive B-cell lymphoma or leukemia (ALL or CLL)
  • The disease is: * Cohort A (non-ALL patients): ** Relapsed or refractory after two or more lines of therapy, including a CD20 antibody, if an indolent lymphoma ** Relapsed or refractory after two or more lines of therapy, including ibrutinib and venetoclax, if CLL ** Relapsed or refractory after two or more lines of therapy, including a CD20 antibody and an anthracycline, and the patient is ineligible for autologous stem cell transplantation, if an aggressive or highly aggressive lymphoma: *** Ineligibility for autologous stem cell transplantation includes non-responsive disease after salvage therapy and failure to mobilize stem cells for transplant * Cohort B (ALL patients) ** Relapsed or refractory after two or more lines of therapy, if ALL
  • Measurable disease by current criteria (Lugano criteria for lymphomas, International Working Group [IWG] criteria for CLL, and detectable disease for ALL)
  • Age >= 3 and =< 75 years
  • Bilirubin less than 2 times (3 times if the patient has Gilbert syndrome) the upper limit of normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 5 times the upper limit of normal
  • Estimated glomerular filtration rate (GFR) >= 50 mL/min
  • Pulse oximetry of >= 90% on room air
  • Karnofsky or Lansky score of >= 70
  • Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician’s assessment (if some effects of chemotherapy are expected to last long term—for example, residual neuropathy, anemia or alopecia—patient is eligible if meeting other eligibility criteria)
  • 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 * Acceptable methods include long-acting reversible contraception (such as intra uterine device, IUD), hormonal contraception (such the pill or depot progestogen injections), barrier methods (such as condoms), or permanent contraception (such as vasectomy or tubal ligation)
  • Patients 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

  • Currently receiving any investigational agents or received any cellular therapies within the previous 6 weeks
  • History of hypersensitivity reactions to murine protein-containing products
  • Pregnant or lactating
  • Active infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus (HTLV)
  • Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • Uncontrolled active bacterial, fungal or other viral infection

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Contact: Carlos Almeida Ramos
Phone: 713-441-1450
Center for Cell and Gene Therapy
Status: ACTIVE
Contact: Carlos Almeida Ramos
Phone: 713-441-1450
Texas Children's Hospital
Status: ACTIVE
Contact: Carlos Almeida Ramos
Phone: 713-441-1450

PRIMARY OBJECTIVE:

I. To evaluate in patients with refractory/relapsed B-cell non-Hodgkin lymphomas (NHL) or leukemia (acute lymphoblastic leukemia [ALL] or chronic lymphocytic leukemia [CLL]) the safety of escalating doses of CD19.CAR-a natural killer T cells (NKTs).

SECONDARY OBJECTIVE:

I. To measure the anti-tumor effects of CD19.CAR-aNKTs in patients with NHL or leukemia.

EXPLORATORY OBJECTIVE:

I. To measure the anti-tumor effects of CD19.CAR-aNKTs in patients with NHL or leukemia.

OUTLINE: This is a dose-escalation study of CD19.CAR-aNKT.

Patients receive cytoreductive chemotherapy consisting of cyclophosphamide three times daily (TID) over 1 hour and fludarabine intravenously (IV) TID over 30 minutes up until 2 weeks before CD19.CAR-aNKT cell infusion. Patients receive CD19.CAR-aNKT IV over 1-10 minutes on day 0.

After completion of study treatment, patents are followed up for 4 weeks, then at 6 weeks, then at months 3, 6, 9, and 12, then every 6 months for 4 years, then annually for 10 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Carlos Almeida Ramos

  • Primary ID ANCHOR
  • Secondary IDs NCI-2021-01068
  • Clinicaltrials.gov ID NCT03774654