About this trial
This study is for patients who have a type of cancer that expresses the protein CD70, which includes lymphoma (lymph gland cancer), myeloma and solid tumors including some sarcomas and kidney cancers, and the cancer has come back or has not gone away after standard of care treatment.
As there are limited or no remaining standard treatments available to treat this cancer, patients are being asked to volunteer to be in a gene transfer research study using special immune cells to create a specialized immune cell that will recognize a protein called CD70 that is expressed on the outside surface of the tumor cells in the body.
This research study combines different ways of fighting disease by using T cells and "arming" them to recognize a specific protein on cancer cells. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. T cells by themselves have been used to treat patients with cancers and have shown promise, but have not been strong enough to cure most patients.
The protein used in this study is called anti-CD70. It has been developed from human CD27 on normal T cells, since it is the natural binding partner that can connect with CD70. This anti-CD70 protein sticks to tumor cells when it binds to CD70. CD70 binders have been used to treat people with different types of cancers. For this study, anti-CD70 has been changed so that instead of floating free in the blood it is now joined to the T cells. When binder is joined to a T cell in this way it is called a chimeric receptor or "CAR T cell". The doctors then made another change to cause these T cells to kill any cell that has CD70. This causes the "CAR T cells" to kill blood cancer cells which are confirmed to have CD70.
In the laboratory, investigators have found that T cells work better if there are proteins added that stimulate T cells. The anti-CD70 (CD27) protein is unique because it can bind to CD70 on tumor cells but also stimulates the T cells that express it. Adding the CD27 makes the cells grow better and may help them to last longer in the body, thus giving the cells a better chance of killing the tumor cells.
These CD70 "CAR" T cells are investigational products not approved by the Food and Drug Administration.
The purpose of this study is to find a dose of CAR T cells that is safe, to learn what the side effects are and to see whether this therapy might help people with lymphoma (lymph gland cancer), myeloma and certain solid tumors including some sarcomas and kidney cancers.
Eligibility criteria
Qualifiers
CD70 positive tumor with at least 26% CD70+ tumor cells by immunohistochemistry (staining can be pending at time of procurement)
Age ≤75 years (except for sarcoma: only patients age ≤25 are eligible) NOTE: The first three (3) patients treated on the study will be adults (≥18 years of age)
Hemoglobin ≥ 7.0 g/dL (can be transfused)
If apheresis required to collect blood, PT and aPTT <1.5x ULN; Serum Creatinine < 2 x ULN; AST < 5 x ULN.
Disqualifiers
Active infection (bacterial, fungal or viral) requiring ongoing treatment without improvement.
Known active infection with HIV or HTLV (collected blood will be sent for HIV/HTLV testing, separate testing prior to procurement not required). Patients with HIV are eligible if viral load is undetectable on therapy and CD4 count is >350 mm3.
Active second cancer (except non-melanoma skin cancer or in situ breast cancer or cervical cancer) or other cancer treated ≤ 2 years prior to enrollment
Ongoing treatment with immune suppression for prophylaxis/treatment of GVHD including high dose steroids (e.g., prednisone > 0.5 mg/kg/day).
Trial design
Treatments tested in this trial
- Dose Level -1
- Dose Level 1 (starting dose level)
- Dose Level 2
- Dose Level 3
Treatment groups
Sponsors and collaborators
Baylor College of Medicine
Lead sponsor
Center for Cell and Gene Therapy, Baylor College of Medicine
Collaborator
The Methodist Hospital Research Institute
Collaborator