Acute Lymphoblastic LeukemiaPhase 1DOTTINCT01494103
Administration of Donor T Cells With the Caspase-9 Suicide Gene
A Phase 1 study testing iCaspase9-transduced T cells and AP1903 in people with Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Patients will be receiving a stem cell transplant as treatment for their disease. As part of the stem cell transplant, patients will be given very strong doses of chemotherapy, which will kill all their existing stem cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Acute Myeloid Leukemia
- What is being tested?
- iCaspase9-transduced T cells and AP1903
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2011to May 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Lack of a suitable conventional donor (i.e. 5/6 or 6/6 related, or 5/6 or 6/6 unrelated donor), or presence of a rapidly progressive disease not permitting time to identify an unrelated donor.
- High risk disease in one of the following:
- Myelodysplastic syndrome (MDS) in one of the following categories: RCMD with an IPSS-R of intermediate, poor, or very poor, RAEB-1, or RAEB-2
- Acute myeloid leukemia (AML) after first relapse or primary refractory disease
- Chronic myelogenous leukemia (CML) in Chronic Phase 2 or greater, Accelerated Phase or Blast Crisis
- Acute lymphoblastic leukemia (ALL) after first relapse or primary refractory disease, or High-Grade Non Hodgkin lymphoma (NHL) Stage III or IV after first relapse or primary refractory disease
Show all 20Show fewer
- Hemophagocytic lymphohistiocytosis (HLH)
- Familial hemophagocytic lymphohistiocytosis (FLH)
- Viral-associated hemophagocytic syndrome (VAHS)
- T or NK cell lymphoproliferative syndrome
- X-linked lymphoproliferative disease (XLP)
- Engrafted with an absolute neutrophil count (ANC) > 500 cells/µL
- Greater than or equal to 50% donor chimerism in either peripheral blood or bone marrow, or relapse of their original disease
- Life expectancy > 30 days
- Lansky/Karnofsky score greater than or equal to 60
- Absence of severe renal disease (creatinine > 2X upper limit of normal for age)
- Absence of severe hepatic disease (direct bilirubin > 3X upper limit of normal or SGOT > 3X upper limit of normal)
- Oxygen saturation > 94% on room air
- Patient/Guardian able to give informed consent
- AP1903 available in sufficient quantities to allow for treatment of the patient
Who cannot join
- GvHD
- Severe intercurrent infection
- Pregnancy*
- Other investigational drugs in the prior 30 days
- Pregnancy test only required for at-risk individuals, defined as female patients of childbearing potential who have received a reduced-intensity conditioning regimen.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Texas Children's Hospital
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
About this study
Official title: Administration of Haploidentical Donor T Cells Transduced With the Inducible Caspase-9 Suicide Gene
Patients will be receiving a stem cell transplant as treatment for their disease. As part of the stem cell transplant, patients will be given very strong doses of chemotherapy, which will kill all their existing stem cells.
A close relative of the patient will be identified, whose stem cells are not a perfect match for the patient's, but can be used. This type of transplant is called "allogeneic", meaning that the cells are from a donor. With this type of donor who is not a perfect match, there is typically an increased risk of developing GvHD, and a longer delay in the recovery of the immune system.
Read more
GvHD is a serious and sometimes fatal side-effect of stem cell transplant. GvHD occurs when the new donor cells (graft) recognize that the body tissues of the patient (host) are different from those of the donor.
In this study, investigators are trying to see whether they can make special T cells in the laboratory that can be given to the patient to help their immune system recover faster. As a safety measure, we want to "program" the T cells so that if, after they have been given to the patient, they start to cause GvHD, we can destroy them ("suicide gene").
Investigators will obtain T cells from a donor, culture them in the laboratory, and then introduce the "suicide gene" which makes the cells sensitive to a specific drug called AP1903. If the specially modified T cells begin to cause GvHD, the investigators can kill the cells by administering AP1903 to the patient. We have had encouraging results in a previous study regarding the effective elimination of T cells causing GvHD, while sparing a sufficient number of T cells to fight infection and potentially cancer.
More specifically, T cells made to carry a gene called iCasp9 can be killed when they encounter the drug AP1903. To get the iCasp9 gene into T cells, we insert it using a virus called a retrovirus that has been made for this study. The 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.
The major purpose of this study is to find a safe and effective dose of "iCasp9" T cells that can be given to patients who receive an allogeneic stem cell transplant. Another important purpose of this study is to find out whether these special T cells can help the patient's immune system recover faster after the transplant than they would have otherwise.
Read the detailed description
If the patient is doing well after the stem cell transplant, and does not have severe GvHD, s/he will be eligible to receive the special "iCasp9" T cells from Day 30 to 90 after transplant. The specially selected and treated T cells will be given by vein (IV) once.
This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose (1 of 5 different levels) of T cells. Once that dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 5 dose levels are studied. If the side-effects are too severe, the dose will be lowered or the T cell injections will be stopped.
If the patient develops GvHD after being given the specially treated T cells, we will prescribe AP1903, which has been shown to kill cells carrying the iCasp9 gene. This drug will be given as a 2-hour IV infusion.
We will continue to follow the patient weekly in the bone marrow transplant clinic for the first month after the infusion, to check for side-effects of the treatment and for GvHD. The patient will have the standard tests performed that all patients have after transplant, even when not receiving special T cells.
- Conditions
- Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, Non Hodgkin Lymphoma, Hemophagocytic Lymphohistiocytosis
- Being tested
- iCaspase9-transduced T cells, AP1903
- Keywords
- Acute lymphoblastic leukemia, Myelodysplastic syndrome, Acute myeloid leukemia, Chronic myelogenous leukemia, Non Hodgkin lymphoma, Hemophagocytic lymphohistiocytosis, Familial hemophagocytic lymphohistiocytosis, Hemophagocytic syndrome, Epstein Barr virus infection, X-linked lymphoproliferative disease
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Non-Hodgkin, Lymphohistiocytosis, Hemophagocytic, Epstein-Barr Virus Infections, Lymphoproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iCaspase9-transduced T cellsBiological
Patients will receive the T cells between 30 and 90 days following transplantation. The T cells will be infused through a catheter line.
AP1903Drug
Also called AP1903 Dimerizer Drug
AP1903 will be administered if there is development of Grade 1 or greater GvHD.
Dose: 0.4 mg/kg by IV over 2 hours.
Up to 3 additional doses may be administered if the GvHD does not respond or gets worse.
| Study group | Role | What they receive |
|---|---|---|
| iCaspase9-transduced T cells | Experimental | The 5 dose levels are:
1. 1 x 10^4 T cells/kg
2. 1 x 10^5 T cells/kg
3. 5 x 10^5 T cells/kg
4. 1 x 10^6 T cells/kg
5. 5 x 10^6 T cells/kg
AP1903 will be administered if there is development of Grade 1 or greater GvHD. Receives: Biological: iCaspase9-transduced T cells; Drug: AP1903 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical and immunological effects of AP1903 administration.
To evaluate the clinical and immunological effects of AP1903 administration, a dimerizer drug used to activate an iCaspase9 suicide gene mechanism, to subjects who have received escalating doses of T lymphocytes expressing the iCaspase9 gene and developed acute graft-versus-host-disease (GvHD).
Measured: 14 days
Secondary outcomes (3)
T cell dose that produces a greater than 25% risk of Grade II or greater GvHD.
To discover the number of T cells/kg (up to 5 x 10^6/kg) that produce a greater than 25% risk of inducing Grade II or greater acute GvHD in these subjects.
Measured: 42 days
Immune reconstitution and relative contribution of iCaspase9-modified T cells post-infusion.
To measure the subsequent immune reconstitution of recipients of iCaspase9 modified T cells (and dimerizer drug), and assess the relative contribution of endogenous T cell recovery and infused gene-modified T cells.
Measured: Up to 15 years
Overall and disease-free survival.
To measure the overall and disease-free survival of recipients of iCaspase9 T cells at 100 days and at 1 year post-transplant.
Measured: 100 days and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2011 (estimated)
- Study startNov 2011
- Primary completionMay 2029 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Helen Heslop, Baylor College of Medicine
- Investigators
- Helen E Heslop, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01494103
- Sponsor's protocol ID
- H-28256-DOTTI
- Other IDs
- DOTTI
- Acronym
- DOTTI
- Status last verified
- Sep 2026
- First submitted
- 15 Dec 2011
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Zhou X, Dotti G, Krance RA, Martinez CA, Naik S, Kamble RT, Durett AG, Dakhova O, Savoldo B, Di Stasi A, Spencer DM, Lin YF, Liu H, Grilley BJ, Gee AP, Rooney CM, Heslop HE, Brenner MK. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood. 2015 Jun 25;125(26):4103-13. doi: 10.1182/blood-2015-02-628354. Epub 2015 May 14.
PubMed 25977584
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Haploidentical Donor T Cells Transduced With the Inducible Caspase-9 Suicide Gene
- ClinicalTrials.gov ID
- NCT01494103
- Acronym / sponsor ID
- DOTTI / H-28256-DOTTI
- Conditions
- Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, Non Hodgkin Lymphoma, Hemophagocytic Lymphohistiocytosis
- Keywords
- Acute lymphoblastic leukemia, Myelodysplastic syndrome, Acute myeloid leukemia, Chronic myelogenous leukemia, Non Hodgkin lymphoma, Hemophagocytic lymphohistiocytosis, Familial hemophagocytic lymphohistiocytosis, Hemophagocytic syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Nov 2011
- Primary completion
- May 2029 (estimated)
- Study completion
- May 2029 (estimated)
- First posted
- 16 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients will be receiving a stem cell transplant as treatment for their disease. As part of the stem cell transplant, patients will be given very strong doses of chemotherapy, which will kill all their existing stem cells.
A close relative of the patient will be identified, whose stem cells are not a perfect match for the patient's, but can be used. This type of transplant is called "allogeneic", meaning that the cells are from a donor. With this type of donor who is not a perfect match, there is typically an increased risk of developing 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 (graft) recognize that the body tissues of the patient (host) are different from those of the donor.
In this study, investigators are trying to see whether they can make special T cells in the laboratory that can be given to the patient to help their immune system recover faster. As a safety measure, we want to "program" the T cells so that if, after they have been given to the patient, they start to cause GvHD, we can destroy them ("suicide gene").
Investigators will obtain T cells from a donor, culture them in the laboratory, and then introduce the "suicide gene" which makes the cells sensitive to a specific drug called AP1903. If the specially modified T cells begin to cause GvHD, the investigators can kill the cells by administering AP1903 to the patient. We have had encouraging results in a previous study regarding the effective elimination of T cells causing GvHD, while sparing a sufficient number of T cells to fight infection and potentially cancer.
More specifically, T cells made to carry a gene called iCasp9 can be killed when they encounter the drug AP1903. To get the iCasp9 gene into T cells, we insert it using a virus called a retrovirus that has been made for this study. The 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.
The major purpose of this study is to find a safe and effective dose of "iCasp9" T cells that can be given to patients who receive an allogeneic stem cell transplant. Another important purpose of this study is to find out whether these special T cells can help the patient's immune system recover faster after the transplant than they would have otherwise.
Detailed description
If the patient is doing well after the stem cell transplant, and does not have severe GvHD, s/he will be eligible to receive the special "iCasp9" T cells from Day 30 to 90 after transplant. The specially selected and treated T cells will be given by vein (IV) once.
This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose (1 of 5 different levels) of T cells. Once that dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 5 dose levels are studied. If the side-effects are too severe, the dose will be lowered or the T cell injections will be stopped.
If the patient develops GvHD after being given the specially treated T cells, we will prescribe AP1903, which has been shown to kill cells carrying the iCasp9 gene. This drug will be given as a 2-hour IV infusion.
We will continue to follow the patient weekly in the bone marrow transplant clinic for the first month after the infusion, to check for side-effects of the treatment and for GvHD. The patient will have the standard tests performed that all patients have after transplant, even when not receiving special T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| iCaspase9-transduced T cells | Experimental | Biological: iCaspase9-transduced T cells, Drug: AP1903The 5 dose levels are: 1. 1 x 10^4 T cells/kg 2. 1 x 10^5 T cells/kg 3. 5 x 10^5 T cells/kg 4. 1 x 10^6 T cells/kg 5. 5 x 10^6 T cells/kg AP1903 will be administered if there is development of Grade 1 or greater GvHD. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- Lack of a suitable conventional donor (i.e. 5/6 or 6/6 related, or 5/6 or 6/6 unrelated donor), or presence of a rapidly progressive disease not permitting time to identify an unrelated donor.
- High risk disease in one of the following:
- Engrafted with an absolute neutrophil count (ANC) > 500 cells/µL
- Greater than or equal to 50% donor chimerism in either peripheral blood or bone marrow, or relapse of their original disease
- Life expectancy > 30 days
Key exclusion criteria (5 listed)
- GvHD
- Severe intercurrent infection
- Pregnancy*
- Other investigational drugs in the prior 30 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iCaspase9-transduced T cellsPatients will receive the T cells between 30 and 90 days following transplantation. The T cells will be infused through a catheter line. | Biological | iCaspase9-transduced T cells |
| AP1903Also: AP1903 Dimerizer DrugAP1903 will be administered if there is development of Grade 1 or greater GvHD. Dose: 0.4 mg/kg by IV over 2 hours. Up to 3 additional doses may be administered if the GvHD does not respond or gets worse. | Drug | iCaspase9-transduced T cells |
Primary outcome
Clinical and immunological effects of AP1903 administration.
Time frame: 14 days
To evaluate the clinical and immunological effects of AP1903 administration, a dimerizer drug used to activate an iCaspase9 suicide gene mechanism, to subjects who have received escalating doses of T lymphocytes expressing the iCaspase9 gene and developed acute graft-versus-host-disease (GvHD).
3 secondary outcomes
T cell dose that produces a greater than 25% risk of Grade II or greater GvHD.
Time frame: 42 days
Immune reconstitution and relative contribution of iCaspase9-modified T cells post-infusion.
Time frame: Up to 15 years
Overall and disease-free survival.
Time frame: 100 days and 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Derived from this study: PubMed 25977584Zhou X, Dotti G, Krance RA, Martinez CA, Naik S, Kamble RT, Durett AG, Dakhova O, Savoldo B, Di Stasi A, Spencer DM, Lin YF, Liu H, Grilley BJ, Gee AP, Rooney CM, Heslop HE, Brenner MK. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood. 2015 Jun 25;125(26):4103-13. doi: 10.1182/blood-2015-02-628354. Epub 2015 May 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen E Heslop, MD principal investigator
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing iCaspase9-transduced T cells and AP1903 in people with Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome, run by Baylor College of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical and immunological effects of AP1903 administration. (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01494103, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.