NCT00710892: CASPALLO

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

Active, enrolled Phase 1 Last updated 8 July 2025

What this trial tests

Phase 1 trial testing Allodepleted T Cells in Acute Lymphoblastic Leukemia in 10 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

1 December 2008

Primary endpoint
1 November 2011

1 July 2026

Quick facts

Lead sponsor	Baylor College of Medicine
Phase	Phase 1
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	1 December 2008
Primary completion	1 November 2011
Estimated completion	1 July 2026
Sites	2 locations across United States

Drugs / interventions tested

• Allodepleted T Cells — full drug profile →

Conditions studied

• Acute Lymphoblastic Leukemia — all drugs for Acute Lymphoblastic Leukemia →
• Non-Hodgkin's Lymphoma — all drugs for Non-Hodgkin's Lymphoma →
• Myelodysplastic Syndrome — all drugs for Myelodysplastic Syndrome →
• Chronic Myeloid Leukemia — all drugs for Chronic Myeloid Leukemia →

Sponsor

Baylor College of Medicine

Who can join

Under 65, any sex, with Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• To determine the maximum number of suicide gene-modified allodepleted donor lymphocytes that can be given to recipients of haploidentical stem cell transplants that will result in a rate of Grade III/IV GVHD of 25% or less.
  Time frame: 45 days
  Maximum tolerated dose of suicide gene-modified allodepleted donor lymphocytes up to a total of 1 x 10e7/kg per dose.

Sponsor's own description

Patients are being asked to participate in this study because they will be receiving a stem cell transplant as treatment for their disease. As part of the stem cell transplant, they will be given very strong doses of chemotherapy, which will kill off all their existing stem cells. Stem cells are created in the bone marrow. They grow into different types of blood cells that we need, including red blood cells, white blood cells, and platelets.

We have identified a close relative of the patients whose stem cells are not a perfect match for the patient, but can be used. This type of transplant is called "allogeneic", meaning that the cells come from a donor. With this type of donor who is not a perfect match, there is typically an increased risk of developing graft-versus-host disease (GvHD) and a longer delay in the recovery of the immune system.

GvHD is a serious and sometimes fatal side effect of stem cell transplant. GvHD occurs when the new donor cells recognize that the body tissues of the patient are different from those of the donor.

In the laboratory, we have seen that cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. To get the iCasp9 into the T cells, we insert it using a virus called a retrovirus that has been made for this study. The drug (AP1903) that will be used to "activate" the iCasp9 is an experimental drug that has been tested in a study in normal donors, with no bad side effects. We hope we can use this drug to kill the T cells. Other drugs that kill or damage T cells have helped GvHD in many studies. However we do not yet know whether AP1903 will kill T cells in humans, even though it has worked in our experimental studies on human cells in animals. Nor do we know whether killing the T cells will help the GvHD. Because of this uncertainty, patients who develop significant GvHD will also receive standard therapy for this complication, in addition to the experimental drug. We hope that having this safety switch in the T cells will let us give higher doses of T cells that will make the immune system recover faster. These specially treated "suicide gene" T cells are an investigational product not approved by the Food and Drug Administration.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inducible apoptosis as a safety switch for adoptive cell therapy.
   Di Stasi A, Tey SK, Dotti G, Fujita Y, et al · · 2011 · cited 1202× · PMID 22047558 · DOI 10.1056/nejmoa1106152
2. Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity.
   Yu S, Yi M, Qin S, Wu K. · · 2019 · cited 208× · PMID 31429760 · DOI 10.1186/s12943-019-1057-4
3. Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene.
   Zhou X, Di Stasi A, Tey SK, Krance RA, et al · · 2014 · cited 135× · PMID 24753538 · DOI 10.1182/blood-2014-01-551671
4. Synthetic biology in the clinic: engineering vaccines, diagnostics, and therapeutics.
   Tan X, Letendre JH, Collins JJ, Wong WW. · · 2021 · cited 72× · PMID 33571426 · DOI 10.1016/j.cell.2021.01.017
5. Hemophagocytic Syndrome and Critical Illness: New Insights into Diagnosis and Management.
   Tothova Z, Berliner N. · · 2015 · cited 70× · PMID 24407034 · DOI 10.1177/0885066613517076
6. Enhancing the safety of CAR-T cell therapy: Synthetic genetic switch for spatiotemporal control.
   Lu L, Xie M, Yang B, Zhao WB, et al · · 2024 · cited 52× · PMID 38394207 · DOI 10.1126/sciadv.adj6251
7. Long-term follow-up for the development of subsequent malignancies in patients treated with genetically modified IECs.
   Steffin DHM, Muhsen IN, Hill LC, Ramos CA, et al · · 2022 · cited 42× · PMID 35325065 · DOI 10.1182/blood.2022015728
8. Engineering Next-Generation CAR-T Cells for Better Toxicity Management.
   Andrea AE, Chiron A, Bessoles S, Hacein-Bey-Abina S. · · 2020 · cited 42× · PMID 33207607 · DOI 10.3390/ijms21228620