Myeloid MalignanciesPhase 1/2NCT06930651
A Phase I/II Study of CAR.70-Engineered IL15-Transduced Cord Blood-Derived NK Cells With TGF-beta Receptor 2 (TGFBR2) Knock Out in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Myeloid Malignancies
A Phase 1/2 study testing Dexamethasone, Cyclophosphamide and Fludarabine in people with Myeloid Malignancies, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the recommended safe dose of TGFBR2 KO CAR27/IL-15 NK cells that can be given to patients with relapsed/refractory disease. The safety and effectiveness of this treatment will also be studied. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Myeloid Malignancies
- What is being tested?
- Dexamethasone, Cyclophosphamide and Fludarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Sep 2025to 1 May 2030
- Phase
- Phase 1/2
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis: Age 18-80 years with diagnosis of:
- Relapsed or refractory AML or "treated secondary AML"
- Patients with a mutation that is targetable with an FDA-approved targeted therapy should have received at least one on these agents. . "Treated secondary AML "includes patients with prior diagnosis of a myeloid neoplasm (e.g. MDS) who received hypomethylating agents for this disease and subsequently progressed to AML. These patients must have received all of the following: a hypomethylating agent + venetoclax and intensive chemotherapy (if a suitable candidate for intensive therapy). These patients may be enrolled at the time of AML diagnosis if they have already received all of the treatments above for their antecedent myeloid neoplasm.
- MDS that is intermediate, high-risk or very-high risk by the Revised International Prognostic Scoring System (R-IPSS)
- Bone marrow blasts must be >5%.
- The disease must have either 1.) not have responded to at least 4 cycles of a hypomethylating agent or 2.) progressed or relapsed, regardless of the number of cycles received
Show all 20Show fewer
- CMML-1 or CMML-2
- Bone marrow blasts must be >5%.
- The disease must have either 1.) not have responded to at least 4 cycles of a hypomethylating agent or 2.) progressed or relapsed, regardless of the number of cycles received
- CD70 expression >10% measured by immunohistochemistry or multiparameter flow cytometry
- Performance status </=2 (ECOG Scale)
- Adequate liver, cardiac, renal and pulmonary function as defined by the following criteria:
- Total serum bilirubin </=2 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the PI
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) </=3 x ULN, unless due to the underlying leukemia approved by the PI
- Serum creatinine </=2x ULN or creatinine clearance >/=30 mL/min
- Left ventricular ejection fraction >/=40% by echocardiogram or MUGA
- Oxygen saturation >/=93% on room air
- Ability to understand and the willingness to sign a written informed consent document
- Willingness to sign informed consent to long-term follow-up on protocol PA17-0483 to fulfill institutional responsibilities to regulatory agencies
- Willingness to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months after completion of study participation. For women of childbearing potential, adequate methods of contraception include: complete abstinence,, hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal Ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide.
Who cannot join
- Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
- Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
- Active central nervous system leukemia
- Known human immunodeficiency virus (HIV) seropositive, unless well-controlled on stable doses of anti-retroviral therapy.
- Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection Note: Patients who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
- Patients with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI
Show all 11Show fewer
- Use of calcineurin inhibitors (e.g. tacrolimus) within the past 2 weeks
- Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before lymphodepletion, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator.
- Prior recent treatment with corticosteroids, hydroxyurea, and/or cytarabine (up to 2 g/m2 given for cytoreduction within the preceding 7 days) is permitted up until 1 day prior to lymphodepletion.
- Patients may continue on non-investigational targeted therapies up until 3 days prior to lymphodepletion.
- Pregnant or breastfeeding women will not be eligible
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030
Nicholas Short, MD, 713-563-4485, nshort@mdanderson.org
Nicholas Short, MD
About this study
The goal of this clinical research study is to find the recommended safe dose of TGFBR2 KO CAR27/IL-15 NK cells that can be given to patients with relapsed/refractory disease. The safety and effectiveness of this treatment will also be studied.
Read the detailed description
This is a phase I/II, two-arm, open-label study. The study will have a phase I dose-escalation portion using a standard "BOIN" approach to determine the MTD of the CAR.70/IL15-transduced/TGFBR2KO CB-NK cells, followed by phase II expansions of 2 arms: 1.) patients with relapsed/refractory AML and 2.) patients with MDS/CMML after HMA failure.
Up to 12 patients will be enrolled in the phase I portion of the study. Following determination of the recommended phase 2 dose (RP2D), 20 patients will be enrolled into the AML arm and 10 patients will be enrolled into the MDS/CMML arm (30 patients total in phase II).
The regimen consists of lymphodepleting and priming chemotherapy with dexamethasone, decitabine, fludarabine and cyclophosphamide, followed by a one-time infusion of the CAR.70/IL15-transduced/TGFBR2KO CB-NK cells
Primary Objectives:
- Phase I: To determine the safety and optimal cell dose of TGFBR2 KO CAR27/IL-15 NK cells in patients with relapsed/refractory myeloid malignances
- Phase II: To determine the response rates of TGFBR2 KO CAR27/IL-15 NK cells in patients with relapsed/refractory AML and in patients with MDS or CMML after HMA failure
Secondary Objectives:
- To determine the CR rate in each cohort
- To determine the rate of flow cytometry MRD negativity (AML cohort only)
- To assess duration of response, relapse-free survival (AML cohort only), and overall survival
- To determine hematologic and non-hematologic toxicities
Exploratory Objectives:
- To assess impact of baseline cytomolecular features and CD70 expression on response
- To quantify persistence of the infused CAR product
- To conduct comprehensive immune reconstitution studies
- Conditions
- Myeloid Malignancies
- Being tested
- Dexamethasone, Cyclophosphamide, Fludarabine, Decitabine, TGFBR2 KO CAR27/IL-15 NK cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Given Orally
CyclophosphamideDrug
Given by IV
FludarabineDrug
Given by IV
DecitabineDrug
Given by IV
TGFBR2 KO CAR27/IL-15 NK cellsBiological
Given by Infusion
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Dose Escalation with CAR.70 | Experimental | Participants will receive lymphodepleting and primary chemotherapy, followed by a one-time infusion of TGFR KO-CAR27/IL-15 NK cells. Dose of the cells will be a different dose until a maximum tolerated dose is found. Receives: Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Decitabine; Biological: TGFBR2 KO CAR27/IL-15 NK cells |
| Phase 2A: Dose Expansion with CAR.70 for AML Patients | Experimental | Participants will receive lymphodepleting and primary chemotherapy, followed by a one-time infusion of TGFR KO-CAR27/IL-15 NK cells using the maximum tolerated dose found in escalation Receives: Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Decitabine; Biological: TGFBR2 KO CAR27/IL-15 NK cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Adverse Events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year
Response rates (AML cohort)
Rate of complete remission (CR) + CR with incomplete hematologic recovery (CRi) + CR with CR with partial hematologic recovery (CRh)
Measured: 30 days from CAR infusion
Response rates (MDS/CMML) cohort
Rate of CR + partial remission (PR) + CR with limited count recovery (CRL), CRh, hematologic improvement (HI) for MDS; rate of CR + PR + marrow CR (mCR) + clinical benefit (CB) for CMML
Measured: 30 days from CAR infusion
Secondary outcomes (6)
CR rate
Rate of CR in each cohort
Measured: 30 days from CAR infusion
Measurable residual disease (MRD) negativity (AML cohort)
Rate of MRD negativity assessed by flow cytometry
Measured: 30 days from CAR infusion
Duration of response
Time from response to relapse
Measured: Through study completion; an average of 1 year
Relapse-free survival
Time from response to relapse or death from any cause
Measured: Through study completion; an average of 1 year
Overall survival
Time from treatment start to death from any cause
Measured: Through study completion; an average of 1 year
Hematologic and non-hematologic toxicities
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 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 Apr 2025
- Study start3 Sep 2025
- Primary completion1 May 2028 (estimated)
- Study completion1 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myeloid MalignanciesStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicholas Short, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06930651
- Sponsor's protocol ID
- 2024-1967
- Other IDs
- NCI-2025-02697
- Status last verified
- Sep 2026
- First submitted
- 9 Apr 2025
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of CAR.70-Engineered IL15-Transduced Cord Blood-Derived NK Cells With TGF-beta Receptor 2 (TGFBR2) Knock Out in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Myeloid Malignancies
- ClinicalTrials.gov ID
- NCT06930651
- Acronym / sponsor ID
- 2024-1967
- Conditions
- Myeloid Malignancies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 3 Sep 2025 (actual)
- Primary completion
- 1 May 2028 (estimated)
- Study completion
- 1 May 2030 (estimated)
- First posted
- 16 Apr 2025 (actual)
- 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.
The goal of this clinical research study is to find the recommended safe dose of TGFBR2 KO CAR27/IL-15 NK cells that can be given to patients with relapsed/refractory disease. The safety and effectiveness of this treatment will also be studied.
Detailed description
This is a phase I/II, two-arm, open-label study. The study will have a phase I dose-escalation portion using a standard "BOIN" approach to determine the MTD of the CAR.70/IL15-transduced/TGFBR2KO CB-NK cells, followed by phase II expansions of 2 arms: 1.) patients with relapsed/refractory AML and 2.) patients with MDS/CMML after HMA failure.
Up to 12 patients will be enrolled in the phase I portion of the study. Following determination of the recommended phase 2 dose (RP2D), 20 patients will be enrolled into the AML arm and 10 patients will be enrolled into the MDS/CMML arm (30 patients total in phase II).
The regimen consists of lymphodepleting and priming chemotherapy with dexamethasone, decitabine, fludarabine and cyclophosphamide, followed by a one-time infusion of the CAR.70/IL15-transduced/TGFBR2KO CB-NK cells
Primary Objectives:
- Phase I: To determine the safety and optimal cell dose of TGFBR2 KO CAR27/IL-15 NK cells in patients with relapsed/refractory myeloid malignances
- Phase II: To determine the response rates of TGFBR2 KO CAR27/IL-15 NK cells in patients with relapsed/refractory AML and in patients with MDS or CMML after HMA failure
Secondary Objectives:
- To determine the CR rate in each cohort
- To determine the rate of flow cytometry MRD negativity (AML cohort only)
- To assess duration of response, relapse-free survival (AML cohort only), and overall survival
- To determine hematologic and non-hematologic toxicities
Exploratory Objectives:
- To assess impact of baseline cytomolecular features and CD70 expression on response
- To quantify persistence of the infused CAR product
- To conduct comprehensive immune reconstitution studies
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Dose Escalation with CAR.70 | Experimental | Drug: Dexamethasone, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Decitabine, Biological: TGFBR2 KO CAR27/IL-15 NK cellsParticipants will receive lymphodepleting and primary chemotherapy, followed by a one-time infusion of TGFR KO-CAR27/IL-15 NK cells. Dose of the cells will be a different dose until a maximum tolerated dose is found. |
| Phase 2A: Dose Expansion with CAR.70 for AML Patients | Experimental | Drug: Dexamethasone, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Decitabine, Biological: TGFBR2 KO CAR27/IL-15 NK cellsParticipants will receive lymphodepleting and primary chemotherapy, followed by a one-time infusion of TGFR KO-CAR27/IL-15 NK cells using the maximum tolerated dose found in escalation |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Diagnosis: Age 18-80 years with diagnosis of:
- CD70 expression >10% measured by immunohistochemistry or multiparameter flow cytometry
- Performance status </=2 (ECOG Scale)
- Adequate liver, cardiac, renal and pulmonary function as defined by the following criteria:
- Ability to understand and the willingness to sign a written informed consent document
Key exclusion criteria (11 listed)
- Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
- Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
- Active central nervous system leukemia
- Known human immunodeficiency virus (HIV) seropositive, unless well-controlled on stable doses of anti-retroviral therapy.
- Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection Note: Patients who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
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 |
|---|---|---|
| DexamethasoneGiven Orally | Drug | Phase 1: Dose Escalation with CAR.70, Phase 2A: Dose Expansion with CAR.70 for AML Patients |
| CyclophosphamideGiven by IV | Drug | Phase 1: Dose Escalation with CAR.70, Phase 2A: Dose Expansion with CAR.70 for AML Patients |
| FludarabineGiven by IV | Drug | Phase 1: Dose Escalation with CAR.70, Phase 2A: Dose Expansion with CAR.70 for AML Patients |
| DecitabineGiven by IV | Drug | Phase 1: Dose Escalation with CAR.70, Phase 2A: Dose Expansion with CAR.70 for AML Patients |
| TGFBR2 KO CAR27/IL-15 NK cellsGiven by Infusion | Biological | Phase 1: Dose Escalation with CAR.70, Phase 2A: Dose Expansion with CAR.70 for AML Patients |
Primary outcome
Safety and Adverse Events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Response rates (AML cohort)
Time frame: 30 days from CAR infusion
Rate of complete remission (CR) + CR with incomplete hematologic recovery (CRi) + CR with CR with partial hematologic recovery (CRh)
Response rates (MDS/CMML) cohort
Time frame: 30 days from CAR infusion
Rate of CR + partial remission (PR) + CR with limited count recovery (CRL), CRh, hematologic improvement (HI) for MDS; rate of CR + PR + marrow CR (mCR) + clinical benefit (CB) for CMML
6 secondary outcomes
CR rate
Time frame: 30 days from CAR infusion
Measurable residual disease (MRD) negativity (AML cohort)
Time frame: 30 days from CAR infusion
Duration of response
Time frame: Through study completion; an average of 1 year
Relapse-free survival
Time frame: Through study completion; an average of 1 year
Overall survival
Time frame: Through study completion; an average of 1 year
Hematologic and non-hematologic toxicities
Time frame: Through study completion; an average of 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 4 Sep 2026.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
Related trials for Myeloid Malignancies
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 2
MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 2
Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases
Acute Leukemia of Ambiguous Lineage, Acute Lymphoblastic Leukemia
RecruitingPhase 1
Imatinib to Increase RUNX1 Activity in Participants With Germline RUNX1 Deficiency
Inherited Bone Marrow Failure Syndrome, Familial Platelet Disorder With Predisposition to Myeloid Malignancies
RecruitingPhase 1/2
Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies
Lymphodepleting Chemotherapy, Myeloid Malignancies
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.
Nicholas Short, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dexamethasone, Cyclophosphamide and Fludarabine in people with Myeloid Malignancies, run by M.D. Anderson Cancer Center at 1 site 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 11 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: looking for participants now, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Nicholas Short, MD ((713) 563-4485, nshort@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Adverse Events (AEs) (time frame: Through study completion; an average of 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.