Hematological MalignancyPhase 1/2NCT05110742
Phase I/II Study of CD5 CAR Engineered IL15-Transduced Cord Blood-Derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Hematological Malignances
A Phase 1/2 study testing Fludarabine Phosphate, Cyclophosphamide and CAR.5/IL15-transduced CB-NK cells in people with Hematological Malignancy, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To determine the safety, efficacy and optimal cell dose of CAR 5/IL15-transduced CB-NK cells in patients with relapsed/refractory T-cell malignances, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematological Malignancy
- What is being tested?
- Fludarabine Phosphate, Cyclophosphamide and CAR.5/IL15-transduced CB-NK cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Apr 2024to 31 Dec 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with hematological malignances with an expression of CD5 in the pre-enrollment tumor sample ≥ 30% measured by immunohistochemistry or flow cytometry.
- Patients must meet diseases specific eligibility criteria (see below)
- Patients should be at least 1 week from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, with the last day of cytotoxic chemotherapy no later than Day-13. Patients may continue tyrosine kinase inhibitors or other targeted therapies until at least three days prior to administration of lymphodepleting chemotherapy, with the last day of tyrosine kinase inhibitors or other targeted therapies no later than Day-9.
- Localized radiotherapy to one or more disease sites are allowed prior the infusion provided that there are additional disease sites that are not irradiated.
- Karnofsky/Lansky Performance Scale > 50%.
- Adequate organ function:
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- Renal: Serum creatinine ≤ 2.0ULN or estimated Glomerular Filtration Rate (eGFR using the CKI-EPI equation) ≥ 30 ml/min/1.73 m2.
- Hepatic: ALT/AST ≤ 3.0 x ULN or ≤ 5 x ULN if documented liver involvement with disease, Total bilirubin ≤ 2.0ULN, except in subjects with Gilbert's Syndrome in whom total bilirubin must be ≤ 3.0 mg/dL. No history of liver cirrhosis.
- Cardiac: Cardiac ejection fraction ≥ 40%, no clinically significant pericardial effusion as determined by an ECHO or MUGA, and no uncontrolled arrhythmias or symptomatic cardiac disease.
- Pulmonary: No clinically significant lung involvement, per PI discretion, pleural effusion, baseline oxygen saturation > 92% on room air.
- Able to provide written informed consent.
- 12-80 years of age.
- English and non-English speaking patients are eligible.
- 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. 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.
- Are willing and able to provide informed consent.
- Disease specific inclusion criteria
- T-cell non-Hodgkin's lymphoma and T-cell acute lymphoblastic leukemia
- Patients with history of T-lymphoid malignancies, defined as acute lymphoblastic leukemia (ALL/T-LBL), Peripheral T-cell lymphoma (PTCL-NOS), MF/SS, Hepatosplenic gamma/delta NHL, AITL, ALCL, or other subtypes of T cell NHL, T-PLL, Mixed phenotypic leukemia (MPAL) with CD5 expression who have received at least 2 lines of standard chemo-immunotherapy or targeted therapy and have measurable persistent disease. For T-ALL active disease defined as (>5% of blasts or positive MRD at a level of >0.1% measured by multiparameter flow cytometry).
- Patients with history of T-lymphoid malignancies as defined above with relapsed disease following standard therapy or a stem cell transplant.
- Chronic lymphocytic leukemia (CLL) Chronic lymphocytic leukemia (CLL) small lymphocytic lymphoma (SLL), Richter's transformation of CLL or SLL who have received at least 2 lines of standard therapy or targeted therapy to include chemoimmunotherapy e.g. FCR, BTK inhibitors and a BCL-2 inhibitor and have persistent disease.
- Mantle cell lymphoma Relapsed or refractory mantle cell lymphoma after 2 lines of standard chemoimmunotherapy including a BTKi.
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.
- Active hepatitis B or C.
- HIV with detectable viral load.
- Presence of active neurological disorder(s).
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- 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 criteria.
- Major surgery <4 weeks prior to first dose of study drug
- Allogeneic SCT or DLI <12 weeks prior to first dose of study drug. Recipients of an allogeneic SCT patients should have discontinued all forms of immunosuppression at least 8 weeks prior enrollment in the study.
- Concomitant use of other investigational agents.
- Concomitant use of other anti-cancer agents.
- Patients receiving systemic steroid therapy at time of NK cell infusion (physiological substitutive doses are allowed) or have received ATG or lymphocyte immune globulin within 14 days or alemtuzumab within 3 months of enrollment.
- Patients receiving immunosuppressive therapy.
- Patients with diminished mental capacity will not be enrolled on the study.
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
M D Anderson Cancer Center
Houston, Texas, 77030
Chitra Hosing, 713-745-3219, cmhosing@mdanderson.org
About this study
To determine the safety, efficacy and optimal cell dose of CAR 5/IL15-transduced CB-NK cells in patients with relapsed/refractory T-cell malignances, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases.
Read the detailed description
Primary objective:
To determine the safety, tolerability and optimal cell dose of iC9/CD5CAR/IL-15 NK cells in patients with relapsed/refractory T-cell malignances, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases.
Secondary Objectives:
- To assess the overall response rate (complete and partial response rates)
- To quantify persistence of infused allogeneic donor iC9/CD5CAR/IL-15 NK cells in the recipient.
- To conduct comprehensive immune reconstitution studies.
- Conditions
- Hematological Malignancy
- Being tested
- Fludarabine Phosphate, Cyclophosphamide, CAR.5/IL15-transduced CB-NK cells
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Fludarabine, Fludara®
Given by IV
CyclophosphamideDrug
Also called Cytoxan®, Neosar®
Given by IV
CAR.5/IL15-transduced CB-NK cellsDrug
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Dose Level | Experimental | CAR.5/IL15-transduced CB-NK cells Dose level 1, 1e7 cryopreserved cells flat dose Dose level 2, 1e8 cryopreserved cells flat dose Dose level 3, 1e9 cryopreserved cells flat dose Dose level 4, 1e10 cryopreserved cells flat dose
All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine. Receives: Drug: Fludarabine Phosphate; Drug: Cyclophosphamide; Drug: CAR.5/IL15-transduced CB-NK cells |
| Phase 2 Dose Level | Experimental | Patients will be randomized between the 2 optimal doses of CAR.5/IL15-transduced CB-NK cells determined by Phase 1.
All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine. Receives: Drug: Fludarabine Phosphate; Drug: Cyclophosphamide; Drug: CAR.5/IL15-transduced CB-NK cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0.
General grading:
Grade 1: Mild: discomfort present with no disruption of daily activity, no treatment required beyond prophylaxis.
Grade 2: Moderate: discomfort present with some disruption of daily activity, require treatment.
Grade 3: Severe: discomfort that interrupts normal daily activity, not responding to first line treatment.
Grade 4: Life Threatening: discomfort that represents immediate risk of death
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 posted8 Nov 2021
- Study start22 Apr 2024
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematological MalignancyStudies 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- chitra hosing, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05110742
- Sponsor's protocol ID
- 2021-0526
- Other IDs
- NCI-2021-10898
- Status last verified
- Aug 2026
- First submitted
- 28 Sep 2021
- Last updated
- 20 Aug 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 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of CD5 CAR Engineered IL15-Transduced Cord Blood-Derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Hematological Malignances
- ClinicalTrials.gov ID
- NCT05110742
- Acronym / sponsor ID
- 2021-0526
- Conditions
- Hematological Malignancy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 22 Apr 2024 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 8 Nov 2021 (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.
To determine the safety, efficacy and optimal cell dose of CAR 5/IL15-transduced CB-NK cells in patients with relapsed/refractory T-cell malignances, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases.
Detailed description
Primary objective:
To determine the safety, tolerability and optimal cell dose of iC9/CD5CAR/IL-15 NK cells in patients with relapsed/refractory T-cell malignances, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases.
Secondary Objectives:
- To assess the overall response rate (complete and partial response rates)
- To quantify persistence of infused allogeneic donor iC9/CD5CAR/IL-15 NK cells in the recipient.
- To conduct comprehensive immune reconstitution studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Dose Level | Experimental | Drug: Fludarabine Phosphate, Drug: Cyclophosphamide, Drug: CAR.5/IL15-transduced CB-NK cellsCAR.5/IL15-transduced CB-NK cells Dose level 1, 1e7 cryopreserved cells flat dose Dose level 2, 1e8 cryopreserved cells flat dose Dose level 3, 1e9 cryopreserved cells flat dose Dose level 4, 1e10 cryopreserved cells flat dose All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine. |
| Phase 2 Dose Level | Experimental | Drug: Fludarabine Phosphate, Drug: Cyclophosphamide, Drug: CAR.5/IL15-transduced CB-NK cellsPatients will be randomized between the 2 optimal doses of CAR.5/IL15-transduced CB-NK cells determined by Phase 1. All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients with hematological malignances with an expression of CD5 in the pre-enrollment tumor sample ≥ 30% measured by immunohistochemistry or flow cytometry.
- Patients must meet diseases specific eligibility criteria (see below)
- Patients should be at least 1 week from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, with the last day of cytotoxic chemotherapy no later than Day-13. Patients may continue tyrosine kinase inhibitors or other targeted therapies until at least three days prior to administration of lymphodepleting chemotherapy, with the last day of tyrosine kinase inhibitors or other targeted therapies no later than Day-9.
- Localized radiotherapy to one or more disease sites are allowed prior the infusion provided that there are additional disease sites that are not irradiated.
- Karnofsky/Lansky Performance Scale > 50%.
Key exclusion criteria (18 listed)
- 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.
- Active hepatitis B or C.
- HIV with detectable 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 |
|---|---|---|
| Fludarabine PhosphateAlso: Fludarabine, Fludara®Given by IV | Drug | Phase 1 Dose Level, Phase 2 Dose Level |
| CyclophosphamideAlso: Cytoxan®, Neosar®Given by IV | Drug | Phase 1 Dose Level, Phase 2 Dose Level |
| CAR.5/IL15-transduced CB-NK cellsGiven by IV | Drug | Phase 1 Dose Level, Phase 2 Dose Level |
Primary outcome
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0.
Time frame: through study completion, an average of 1 year
General grading: Grade 1: Mild: discomfort present with no disruption of daily activity, no treatment required beyond prophylaxis. Grade 2: Moderate: discomfort present with some disruption of daily activity, require treatment. Grade 3: Severe: discomfort that interrupts normal daily activity, not responding to first line treatment. Grade 4: Life Threatening: discomfort that represents immediate risk of death
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 20 Aug 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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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.
chitra hosing 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 Fludarabine Phosphate, Cyclophosphamide and CAR.5/IL15-transduced CB-NK cells in people with Hematological Malignancy, 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 22 inclusion and 18 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 20 Aug 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 Chitra Hosing ((713) 745-3219, cmhosing@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0. (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?
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 20 Aug 2026.