Chimeric Antigen Receptor T-cells for The Treatment of AML Expressing CLL-1 Antigen

Acute Myeloid Leukemia Clinical Trial

Official title: Chimeric Antigen Receptor T-cells for The Treatment of Acute Myeloid Leukemia Expressing CLL-1 Antigen

Status Recruiting

Clinical Trial Summary

Patients eligible for this study have a type of blood cancer Acute Myeloid Leukemia (AML) which has come back or has not gone away after treatment.

The body has different ways of fighting disease and infection, and this research study combines two different ways of fighting cancer with antibodies and T cells with the hope that they will work together. T cells (also called T lymphocytes) are special infection-fighting blood cells that can kill other cells including tumor cells. Antibodies are types of proteins that protect the body from bacterial and other infectious diseases. Both antibodies and T cells have been used to treat patients with cancers; they have shown promise, but have not been strong enough to cure most patients when used alone.

T lymphocytes 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 targets CLL-1. This antibody sticks to AML cells because of a substance (protein) on the outside of these cells called CLL-1. For this study, the antibody to CLL-1 has been changed so that instead of floating free in the blood, it is now joined to the T cells. When T-cells contain an antibody that is joined to them, they are called chimeric antigen receptor T-cells or CAR-T cells.

In the laboratory, the investigators have also found that T cells work better if proteins that stimulate T cells are also added, 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. In this study we are going to attach the CLL-1 chimeric receptor that has CD28 added to it to the patient's T cells. We will then test how long the cells last.

These CLL-1 chimeric antigen receptor T cells with CD28 are investigational products not approved by the Food and Drug Administration.

Clinical Trial Description

To make the CLL1-CD28 chimeric antigen receptor T cells, the investigators will collect the patient's blood and stimulate them with growth factors to make the cells grow. To get the CLL-1 antibody and CD28 to attach to the surface of the T cell, we put the antibody gene into the T cell. This is done using a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell. This virus also helps investigators find the T cells in the patient's blood after they are injected. Because the patient will receive cells with a new gene in them the patient will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.

When the patient enrolls on this study, the patient will be assigned a dose of CLL-1 chimeric antigen receptor- T cells. Several studies suggest that the T cells that we give to the patient need room to be able to grow and work well and that this may not happen if there are too many other T cells already circulating in the patient's body. Because of that, the patient will receive two chemotherapy medications before receiving the CLL-1 chimeric antigen receptor- T cells.

One medication is called cyclophosphamide and and the other will be either fludarabine or clofarabine. The patient will receive 3 daily doses of each drug, finishing at least one day before receiving the chimeric antigen receptor- T cells. These drugs will lower the numbers of the patient's T cells before we give them the CLL-1 chimeric antigen receptor T cells and will also help lower the number of other cells that may block the chimeric antigen receptor-T cells from working well. Although we do not expect any effect on the patient's cancer with the doses that will be received, these drugs are part of many treatment plans that are used to treat leukemia.

Patients will be given an injection of cells into the vein through an IV at the assigned dose at a minimum of 24 hours after completing the chemotherapy medications. The injection will take from 1 to 10 minutes. Before patients receive the injection, they may be given a dose of Benadryl and Tylenol. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.

If the patient is one of the first set of enrolled patients, they will be admitted as an inpatient for at least 72 hours so that the doctor and nurses can watch them closely in case any potential side effects occur following infusion. After discharge from the hospital you will be followed closely in the clinic, and will have to remain in the Houston area for at least 4 weeks after the infusion. If patients have any side effects, they may have to be admitted to the hospital for evaluation and management. If after a 4 week evaluation period following the infusion, the patient has achieved a complete response, his/her cancer doctors may decide if you should go on to have a bone marrow transplant, at which time the patient will be removed from the treatment portion of the study

BEFORE BEING TREATED, PATIENTS WILL RECEIVE A SERIES OF STANDARD MEDICAL TESTS:

• Physical exam and History

• Blood tests to measure blood cells, kidney and liver function

• Pregnancy test for female patients who are of child bearing potential -Measurements of your tumor by bone marrow studies

• Imaging such as PET scans, CT scans or MRIs will be obtained if needed

PATIENTS WILL RECEIVE STANDARD MEDICAL TESTS DURING TREATMENT AND AFTER:

• Physical exams and History

• Blood tests to measure blood cells, kidney and liver function

• Measurements of your tumor by bone marrow studies 4-6 weeks after the infusion, possibly 12 weeks after the infusion and then per standard of care.

• Imaging such as PET scans, CT scans or MRIs will be obtained if needed 4-6 weeks following the infusion

To learn more about the way the CLL-1 chimeric receptor-T cells are working and how long they last in the body, extra blood will be drawn. The total amount on any day is about 10 teaspoons (50 mL) or no more than 3 mL per 2.2 pounds body weight in children. This amount is considered safe but may be lowered if you are anemic. This blood may be taken from a central line if you have one. Blood will be taken before the chemotherapy drugs, before the T cell infusion, several hours after the T cell infusion, at 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, and 8 weeks after the infusion, at 3 months, 6 months, 9 months, at 1 year, every 6 months for 4 years, then yearly for a total of 15 years.

If patients have a bone marrow exam while they are on this study, we may ask to have a sample of bone marrow to look for CLL-1 chimeric receptor- T cells.

If a patient decides to withdraw at any time during the study, both samples and data collected during his/her participation will be kept. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

• NCT number: NCT04219163
• Study type: Interventional
• Source: Baylor College of Medicine
• Contact: LaQuisa Hill, MD
• Phone: 713-441-1450
• Email: LaQuisa.Hill@bcm.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: July 9, 2020
• Completion date: July 31, 2038