Allodepleted T Cells for Leukemia

(CASPALLO Trial)

Not currently recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Other investigational drugs

Disqualifiers: Pregnancy, GvHD, Severe infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with certain types of leukemia and other blood disorders undergoing a stem cell transplant. The treatment uses donor T cells modified to include a "suicide gene," which can be activated to eliminate the T cells if they cause graft-versus-host disease (GvHD). Known as Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene, this approach aims to accelerate immune system recovery post-transplant without increasing GvHD risk. The trial seeks patients who have relapsed or have leukemia unresponsive to other treatments and lack a perfectly matched stem cell donor. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot have taken other investigational drugs in the 30 days before the T cell infusion.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using specially modified T cells with a gene called inducible caspase 9 (iCasp9) might offer a safer option. This gene acts like a switch, enabling doctors to eliminate these cells if they cause issues, such as graft-versus-host disease (GvHD), a potential complication after stem cell transplants.

A study on the drug AP1903, which activates this safety switch, found no harmful side effects in healthy volunteers, suggesting it is well-tolerated. However, it remains uncertain whether AP1903 will effectively remove T cells in humans or help manage GvHD. Due to this uncertainty, participants in this trial who develop significant GvHD will also receive standard treatments for the condition.

These specially treated T cells are still under investigation and have not yet received FDA approval. While early results are promising, the safety of this treatment in humans continues to be studied. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about allodepleted T cells transduced with the inducible caspase 9 suicide gene for leukemia because they offer a novel approach to treatment. Unlike traditional chemotherapy or targeted drugs that attack cancer cells directly, this therapy uses genetically engineered T cells to enhance the immune system's ability to target and destroy cancer cells. The unique feature here is the inducible caspase 9 suicide gene, which acts as a safety switch, allowing doctors to eliminate the T cells if they cause adverse reactions. This innovative mechanism provides a promising balance between effective treatment and patient safety, which is a significant advance over existing therapies.

What evidence suggests that allodepleted T cells with the iCasp9 suicide gene might be an effective treatment for leukemia?

Research has shown that specially modified T cells, known as allodepleted T cells, can enhance the safety of stem cell transplants. In this trial, participants will receive allodepleted T cells transduced with an inducible caspase 9 suicide gene. This gene provides a "safety switch" within the T cells. If necessary, the switch can be activated with a drug called AP1903 to safely eliminate the T cells. Studies have found that these cells can aid in faster immune system recovery post-transplant and offer protection against infections. In lab and animal studies, these cells have also reduced complications such as graft-versus-host disease (GvHD), a common risk with stem cell transplants. Although this technology remains in the early stages, it shows promise for improving the safety and effectiveness of transplants. ^{1 2 3 4 6}

Who Is on the Research Team?

Malcolm K Brenner, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with certain blood disorders like leukemia, who are getting a stem cell transplant and have no perfect match donor. They should not be pregnant, must have a life expectancy over 30 days, stable liver and kidney function, good oxygen levels without assistance, and an ability to consent. It's not for those with severe infections or recent other investigational drug use.

Inclusion Criteria

I don't have a closely matched donor or my disease is worsening too quickly.

My transplant shows at least 50% donor cells, or my original disease has returned.

Engrafted with ANC greater than 500

Exclusion Criteria

I have graft-versus-host disease.

You have taken any experimental drugs within the last 30 days.

I do not have a severe ongoing infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Treatment

High-dose chemotherapy to prepare the body for transplantation

Varies

Stem Cell Transplantation

Patients receive haploidentical stem cell transplantation

1 day

T Cell Infusion

Specially selected and treated T cells are infused between Day 30 and Day 90 post-transplant

60 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for GvHD and the effects of AP1903

1 year

Long-term Follow-up

Participants are followed for long-term side effects of the gene transfer

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene

Trial Overview The study tests allodepleted T cells modified with the iCasp9 'suicide gene' in patients receiving non-matched stem cell transplants. If GvHD occurs—a common serious side effect—the modified T cells can be targeted and killed using the experimental drug AP1903 to prevent harm.

How Is the Trial Designed?

Group I: Dose Level 1-3 Experimental Treatment 1 Intervention

Administration of suicide gene-modified allodepleted T cells.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Published Research Related to This Trial

Engineered natural killer T cells (NKT) expressing a functional T-cell receptor (TCR) demonstrated effective antitumor activity in mouse models without causing graft-versus-host disease, suggesting a safer alternative for adoptive T-cell therapy.

The study revealed that the engineered TCR can displace the invariant TCR (iTCR) in NKT cells, allowing for effective targeting of cancer cells while minimizing the risk of autoreactivity, making these cells promising candidates for 'off-the-shelf' immunotherapy products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A High-Avidity T-cell Receptor Redirects Natural Killer T-cell Specificity and Outcompetes the Endogenous Invariant T-cell Receptor. Landoni, E., Smith, CC., Fucá, G., et al.[2020]

In a small trial, T cells modified to target the Wilms tumor antigen 1 were effective in preventing relapse in patients with acute myeloid leukemia after they underwent an allogeneic stem-cell transplant.

This approach highlights the potential of engineered T cell therapies in enhancing post-transplant outcomes for leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCR Gene Therapy Improves AML Prognosis. [2020]

The study explores the use of an inducible caspase 9 (iC9) suicide gene in CAR-T cells to enhance safety by allowing for the elimination of malignant CAR+ B cells, which can arise during treatment manufacturing.

In both in vitro and animal models, the activation of the iC9 suicide gene with the small molecule AP1903 effectively eliminated CAR+ leukemia and lymphoma cells, suggesting a promising strategy to mitigate adverse effects associated with CAR-T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inclusion of the Inducible Caspase 9 Suicide Gene in CAR Construct Increases Safety of CAR.CD19 T Cell Therapy in B-Cell Malignancies. Guercio, M., Manni, S., Boffa, I., et al.[2022]

Adoptive T-cell therapy shows promise for treating various cancers and infections, but safety concerns remain due to potential on-target and off-target toxicities, which can sometimes be fatal.

The inducible caspase 9 (iCasp9) safety switch offers a solution by allowing for the rapid elimination of modified T cells if adverse effects occur, enhancing the safety of T-cell therapies, especially in cases like graft-versus-host disease in stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive T-cell therapy: adverse events and safety switches. Tey, SK.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00710892?cond=Suicide%20gene&viewType=Table&rank=8

Allodepleted T Cells Transduced With Inducible Caspase 9 ... Patients are being asked to participate in this study because they will be receiving a stem cell transplant as treatment for their disease.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2040267/

Inducible caspase 9 suicide gene to improve the safety of ... RESULTS. Selectively allodepleted T cells could be efficiently transduced with iCasp9 and expanded. Selective allodepletion was performed in accordance with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4481597/

Inducible caspase-9 suicide gene controls adverse effects ... Alloreplete iC9-T cells can promote immune recovery posttransplant and protect patients against viral infections. iC9-T cells can be eliminated from both ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00710892

Study Details | NCT00710892 | CASPALLO: Allodepleted T ... CASPALLO: A Phase I Study Evaluating the Use of Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene After Haploidentical Stem Cell ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S000649712040076X

Long-term outcome after haploidentical stem cell transplant ... Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene.

6. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2014.00235/full

The inducible caspase-9 suicide gene system as a “safety ... An inducible Caspase 9 (iCasp9) “safety switch” offers a solution that allows for the removal of inappropriately activated CAR T cells.