AzTrials
AzTrials

Lymphodepleting ChemotherapyPhase 1/2NCT06383572

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

A Phase 1/2 study testing Cyclophosphamide, Fludarabine phosphate and Decitabine in people with Lymphodepleting Chemotherapy and Myeloid Malignancies, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

To find a recommended dose of PRAME-TCR-NK cells that can be given to patients with AML or MDS. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Cyclophosphamide, Fludarabine phosphate and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
26 Jun 2024to 1 Apr 2029
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

  • 18- 80 years of age. English and non-English speaking patients are eligible.
  • Patients with one of the following hematological malignances: AML, MDS/CMML. Patients must meet disease specific eligibility criteria (see below)
  • Patients at least 7 days from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, except for Hydroxyurea which is allowed for peripheral blood count control in AML patients until the day prior to administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until up to three days prior to administration of lymphodepleting chemotherapy.
  • Localized radiotherapy to one or more disease sites is allowed prior the infusion provided that there are additional disease sites that are not irradiated to assess response.
  • Karnofsky Performance Scale > 50%.
  • Adequate organ function: as described in 7-10
Show all 30Show fewer
  • Renal: Serum creatinine </= 2.0 mg/dL and estimated Glomerular Filtration Rate (eGFR using the CKD-EPI equation).GFR = 141 x [min(Scr/k), 1)a x max (Scr/k), 1) -1.209] x Age-0.993 x 1.018 [if female] x [ 1.157 if Black] (a is 0.329 for females and 0.411 for males; min indicates minimum of Scr/k or 1, and max indicates maximum of Scr/k or 1)
  • Hepatic: ALT/AST </= 2.5 x ULN or </= 5 x ULN if documented liver metastases, Total bilirubin </= 1.5 mg/dL, except in subjects with Gilbert's Syndrome in whom total bilirubin must be </= 3.0 mg/dL. No history of liver cirrhosis. No ascites.
  • Cardiac: Cardiac ejection fraction >/= 40%, no clinically significant pericardial effusion as determined by an ECHO/MUGA, and no uncontrolled arrhythmias or symptomatic cardiac disease.
  • Pulmonary: No clinically significant pleural effusion (per PI discretion), baseline oxygen saturation > 92% on room air and adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) >50%.
  • Able to provide written informed consent.
  • All participants who are able to have children must practice effective birth control while on study and up to 3 months post completion of study therapy. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence, for the length of the study. If the participant is a female and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during this study, she will be taken off this study.
  • Approved methods of birth control are as follows: 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. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physicaian immediately.
  • Men treated or enrolled on this protocol must also agree to use adequate contraception, such as subject post vasectomy, partner with implantable or oninjectable contraceptives, and condoms plus spermicide, prior to the study, for the duration of study participation, and 4 months after completion of study agent administration. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.
  • Signed consent to long-term follow-up protocol PA17-0483 to fulfill the institutional responsibilities to various regulatory agencies.
  • Life Expectancy >=3 mo, by PI assessment
  • Patients are HLA-A*02:01 positive on HLA typing.
  • Patients must have one of the following diseases:
  • Acute myeloid leukemia (AML): one of the following:
  • 1. Patients with active (>5% of blasts or positive MRD at a level of >0.1% measured by multiparameter flow cytometry) relapsed or refractory AML. Who have received at least two lines of therapy. One or more of the lines of therapy must include hypomethylating agents and venetoclax. Patients who have mutations for which there are FDA approved targeted therapies (i.e. FLT3) must also have received at least one of such agent. Patients with diagnosis of acute promyelocytic leukemia are not eligible. Patients who relapse after allogeneic stem cell transplantation are eligible irrespective of the number and type of therapy received prior transplant.
  • Relapsed AML is defined as patients who had a first complete remission (CR) before developing recurrent disease.
  • Refractory AML is defined as patients that have not achieved a CR after 2 cycles of standard induction chemotherapy.
  • OR determining the eligibility of the patient. For example, patients who received hypomethylating agents and venetoclax for the treatment of the MDS are not required to receive again hypomethylating agents and venetoclax to treat the secondary AML to be eligible. Similarly, patients who received two lines of therapy for the management of the MDS or MPD are not required to receive an additional two lines of therapy for the management of the AML to be eligible. Patients who relapse after allogeneic stem cell transplantation are eligible irrespective of the number and type of therapy received prior transplant.
  • Myelodysplastic syndromes (MDS)/Chronic myelomonocytic leukemia (CMML):one of the following:
  • Patients with high risk or intermediate risk MDS/CMML who have received at least two lines of therapy and have positive MRD at a level of >0.1% measured by multiparameter flow cytometry or are not in morphological remission.
  • OR
  • Patients with relapse high risk or intermediate risk MDS/CMML after at least 2 lines of therapy. Relapse is defined as positive MRD at a level of >0.1% measured by multiparameter flow cytometry or loss of morphological remission.
  • OR
  • CMML patients with refractory disease defined as failure to achieve complete remission after 4 therapy cycles of hypomethylating agent therapy or relapse or progression after any number of cycles of therapy.
  • Patients with MDS/CMML who relapse after allogeneic stem cell transplantation are eligible irrespective of the number and type of therapy received prior to transplant.

Who cannot join

  • Positive beta HCG in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
  • Presence of clinically significant Grade 3 or greater toxicity from the previous treatment, as determined by PI.
  • Presence of uncontrolled fungal, bacterial, viral, or other infection not responding to appropriate therapy.
  • Known active hepatitis B or C.
  • Known HIV with detectable viral load
  • Presence of active neurological disorder(s).
Show all 32Show fewer
  • Active autoimmune disease within 12 months of enrollment
  • Active cerebral or meningeal involvement by the malignancy
  • Active (defined as requiring therapy) acute or chronic GVHD
  • Any other malignancy known to be active, except for treated cervical intra-epithelial neoplasia and non-melanoma skin cancer.
  • Presence of any other serious medical condition that may endanger the patient at investigator discretion.
  • Major surgery <4 weeks prior to first dose of the preparatory chemotherapy
  • Allogeneic SCT or DLI <12 weeks prior to first dose of preparatory chemotherapy
  • Concomitant use of other investigational agents.
  • Concomitant use of other anti-cancer agents.
  • Patients receiving systemic steroid therapy at time of enrollment (physiological substitutive doses deemed per PI assessment are allowed),or have received antithymocyte globulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumab within 28 days of enrollment.
  • Patients receiving immunosuppressive therapy such as steroids and calcineurin inhibitors.
  • Criteria to Receive Lymphodepletion Chemotherapy:
  • Within 72 hours prior to the start of Lymphodepletion chemotherapy, subjects must meet the eligibility criteria outlined below:
  • No uncontrolled active systemic infection. Subjects must be fever free for at least 48 hours without antipyretics unless the patient is felt to have tumor fever.
  • Absence of clinically significant Grade 3 or greater toxicity from the previous treatment, as determined by the Principal Investigator.
  • Patient should not be receiving systemic steroids above physiologic dosing (excluding dexamethasone 25mg/m^2 PO as noted in the treatment plan from Day -10 through Day -6.) or calcineurin inhibitors.
  • Patients should be at least 7 days from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, except for Hydroxyurea which is allowed for peripheral blood count control in AML patients until the day prior to administration of lymphodepleting chemotherapy.
  • Patients may continue tyrosine kinase inhibitors or other targeted therapies until up to three days prior to administration of lymphodepleting chemotherapy
  • Criteria Prior to NK Cell Infusion:
  • On Day 0, prior to the NK Cell infusion, subjects must meet the eligibility criteria for infusion outlined
  • No active and uncontrolled systemic infection. Subjects must be fever free for 48 hours without antipyretic unless patient is felt to have tumor fever.
  • No clinical signs of cardiac failure.
  • Oxygen saturation levels (SPO2) >92%
  • No other ongoing medical condition that in the opinion of the investigator can affect patient's safety.
  • No rapidly progressing AML/MDS.
  • Patient must be able to be off of all steroid treatment within 24hrs of cell infusion.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jeremy Ramdial, MD contact

(713) 745-0146

jlramdial@mdanderson.org

United States1 site, 1 recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Jeremy Ramdial, MD, 713-745-0146, jlramdial@mdanderson.org

    Jeremy Ramdial, MD

    Recruiting

Other trials in United States

About this study

To find a recommended dose of PRAME-TCR-NK cells that can be given to patients with AML or MDS.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess dose-limiting toxicity (DLT) and determine the safety, day 30 response rate, day 180 treatment failure rate (defined as disease progression or death) and optimal cell dose of T cell receptor (TCR) modified cord blood-natural killer (CB-NK) cells (TCR-NK) targeting PRAME in patients with relapsed/refractory myeloid malignances, for each of the following diseases; AML, and MDS/CMML. The day 30 response rate and day 180 treatment failure rate will be estimated, and the estimates will be used to identify an optimal dose of PRAME-TCR-NK cells.

SECONDARY OBJECTIVES:

  1. To assess the preliminary efficacy of PRAME-TCR-NK cells (day+ 30 complete and partial response rates; day 180 progression-free survival rate) in patients with relapsed/refractory AML and MDS.

II. To quantify persistence of infused allogeneic donor PRAME-TCR CB-derived NK cells in the recipient as an integrated evaluation.

III. To conduct comprehensive immune reconstitution studies.

IV. To obtain preliminary data on quality of life and patient experience (Patient Reported Outcomes Measurement Information Systems [PROMIS]-29 quality of life questionnaire score).

OUTLINE:

This is a phase I dose-escalation study of PRAME-TCR-NK followed by a phase II study.

Patients receive dexamethasone orally (PO) on days -10, -9, -8, -7, and -6, decitabine intravenously (IV) over 1 hour on days -6, -5, and -4, fludarabine IV over 30 minutes and cyclophosphamide IV over 60 minutes on days -5, -4, and -3 and PRAME-TCR-NK cells IV over 2-20 minutes on day 0. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and computed tomography (CT) or chest x-ray pre-treatment and bone marrow aspiration and biopsy, and blood sample collection throughout the study.

After completion of study treatment, patients are followed up for 24 months then for at least 15 years per protocol PA17-0483.

Sponsor: M D Anderson Cancer Center

Lead Organization: M D Anderson Cancer Center

Principal Investigator: Ramdial, Jeremy

Responsible Party: Sponsor

Overall Official: Ramdial, Jeremy (Principal Investigator), M D Anderson Cancer Center

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT06383572
Study groupRoleWhat they receive
Phase 1 (Dose Escalation and Dose Expansion)ExperimentalParticipants will be assigned to a dose level of the NK cell treatment based on when you join this study. Up to 4 dose levels of the treatment will be tested. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the NK cell treatment is found.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine phosphate; Drug: Decitabine; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2024
  2. Study start26 Jun 2024
  3. Primary completion1 Apr 2027 (estimated)
  4. Study completion1 Apr 2029 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06383572
Sponsor's protocol ID
2024-0196
Other IDs
NCI-2024-03505
Status last verified
Oct 2026
First submitted
22 Apr 2024
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide, Fludarabine phosphate and Decitabine in people with Lymphodepleting Chemotherapy and 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 30 inclusion and 32 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 26 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 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 Jeremy Ramdial, MD ((713) 745-0146, jlramdial@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.). 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 NCT06383572.

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 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in