NANT 2021-01 STING trial

NANT 2021-01:  STING Trial: Allo NK with chemoimmunotherapy

Study: NANT 2021-01

Protocol Title: Phase II Study of Ex-Vivo Expanded Allogeneic Universal Donor TGFβi NK Cell Infusions in Combination with Temozolomide, Irinotecan, Dinutuximab, and Sargramostim in Patients with Relapsed or Refractory Neuroblastoma

The STING (Sequential Temozolomide, Irinotecan, NK cells and GD2 mAb) Trial 

Protocol Co-Chairs: Keri Streby, MD Nationwide Children’s Hospital  

  Mark Ranalli, MD Nationwide Children’s Hospital 

For more information about this trial, visit clinicaltrials.gov

What is this Study About

Currently there are very few effective treatments for high-risk neuroblastoma that has returned or that has not responded to treatment.

One treatment that works relatively well for this type of neuroblastoma is a combination of four medicines (dinutuximab, temozolomide, irinotecan, and GM-CSF). Dinutuximab is an antibody that attacks neuroblastoma cells. Temozolomide and irinotecan are two chemotherapy medicines. GM-CSF helps to boost your immune system. This study is trying to learn if this treatment, which is called chemoimmunotherapy, can work better by adding NK cells.

Your immune system is made up of different cell types. One type of immune cell is the natural killer (NK) cell. NK cells use the body’s defense (immune) system to kill neuroblastoma cells. NK cells are only present in the body in small numbers and often your own NK cells don’t work very well against your tumor because neuroblastoma releases chemicals that weaken the NK cells. One of these chemicals is called TGF-beta.

This study uses a newer process to make specially chosen donated NK cells which may work better than your own NK cells. This new type of donated NK cells are called TGF-beta imprinted, which may be better “killers” of tumors like neuroblastoma because they have already been exposed to TGF-beta while they are being prepared and grown. The special NK cells for this study have already been collected from donors selected for this study and are stored for use. Prior studies have used these types of NK cells or similar NK cells for other tumors or neuroblastoma.

Once treatment begins, you will receive temozolomide and irinotecan for 5 consecutive days, with the addition of dinutuximab daily on days 2-5. If you tolerate this chemoimmunotherapy, you will receive the donor TGF-beta NK cells on day 8. You can have this treatment for up to 6 cycles total.

This is a phase II study. This means the main goal is to look at how well you respond to the treatment. The dose of NK cells will remain the same across the study.

Why is this Study Being Done?

The purpose of this research is:

• To see if your tumor gets smaller after the treatment regimen [chemoimmunotherapy plus a special type of natural killer (NK) cells]

• To describe the side effects of the treatment regimen

• To learn how well the treatment is working by looking at your immune cells and the NK cells that were given to you

Criteria That Needs to be Met to Participate in this Study

• You must be 31 years of age or younger

• You must have high-risk neuroblastoma with either refractory or relapsed disease. You may require a biopsy prior to enrollment.

• You must have adequate heart, kidney, liver, lung and bone marrow functions.

• If you have a history of neuroblastoma in the brain or spine, you must have this successfully treated before beginning this study. If you have tumor in the bones around the skull, you are able to participate.

Criteria that Would Make Patients Ineligible to Participate in this Study

• You have a history of having a bad reaction to dinutuximab and your doctor thinks you are unable to tolerate dinutuximab.

• You have a history of progressive disease with irinotecan, temozolomide, dinutuximab, and GM-CSF.

• You have had a stem cell transplant from another donor or an organ transplant or total body irradiation.

• You do not wish to participate in the NANT Biology Study.

• You are pregnant, breast feeding or unwilling to use effective contraception during the study.

• You are on immunosuppressive medications (e.g. tacrolimus, cyclosporine, etc).

• You have an active or uncontrolled infection.

• You are on hemodialysis .

Treatment

Each treatment course is 21 days or longer if your body needs more recovery and you may receive up to six courses of therapy if you are tolerating the treatment and your disease has not gotten worse. You will receive oral or IV temozolomide and IV irinotecan on day 1 through 5 and will receive IV dinutuximab on days 2-5 followed by GM-CSF injections on days 6-12 and a dose of NK cells on day 8. You will have your neuroblastoma evaluated by bone marrow tests and scans before you start this treatment and at the end of cycles 2, 4 and 6.