Chronic Myelomonocytic LeukemiaPhase 1NCT06071624
Chimeric Antigen Receptor T Cell Therapy Redirected to CD4 (CD4CAR)as a Second Line Treatment for Chronic Myelomonocytic Leukemia, CMML.
A Phase 1 study testing CD4CAR in people with Chronic Myelomonocytic Leukemia, run by Huda Salman at 4 sites in United States.
Trial summary
This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-directed chimeric antigen receptor engineered T-cells (CD4CAR) in subjects with relapsed or refractory CMML. Specifically, the study will evaluate the safety and feasibility of CD4CAR T-cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myelomonocytic Leukemia
- What is being tested?
- CD4CAR
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- 21 Feb 2024to Dec 2043
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- ≥ 18 years old at the time of informed consent
- Ability to provide written informed consent and HIPAA authorization
- Diagnosis of CMML that is CD4+ and is recurrent or refractory to first line standard of care treatment.
- Creatinine clearance of ≥ 60 ml/min (or otherwise non clinically significant, per study investigator)
- ALT/AST < 3 x ULN
- Bilirubin < 2 x ULN
Show all 9Show fewer
- No supplemental oxygen at rest Note: Pulmonary Function Test (PFT) only required per treating physician discretion.
- Adequate cardiac function with EF of ≥50%. This will not have to be repeated if within 45 days of initial assessment
- Adequate venous access for apheresis and no other contraindications for leukapheresis
Who cannot join
- CD4 negative CMML
- Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential (see definition below) must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites' clinical policy
- Uncontrolled active infection necessitating systemic therapy
- Active hepatitis B or hepatitis C infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative HCV RNA results exceed the lower detection limit
- Note the following subjects will be eligible:
- Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months prior to enrollment are eligible
Show all 51Show fewer
- Subjects seropositive for HBS antibodies due to hepatitis B virus vaccine with no signs or active infection (Negative HBs Ag, HBc and HBe Ags) are eligible
- Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible
- If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative
- Concurrent use of systemic glucocorticoids in greater than replacement doses or steroid dependency defined in rheumatological and pulmonary diseases as uninterrupted corticosteroid intake for more than a year at a dosage of 0.3 mg/kg/day or greater, and where the underlying disease worsens on temporary stoppage of steroid therapy, with symptoms of steroids withdrawal (eg, lethargy, headache, weakness, pseudo rheumatism, emotional disturbances, etc) precipitated by the temporary stoppage unless tapering can occur safely without compromising the underlying disease, the withdrawal tolerance and can happen in a timeframe appropriate to enroll in this trial without safety concerns
- Subjects who receive daily corticosteroids in replacement doses can be included in the study. The replacement doses are defined as following:
- Hydrocortisone 25mg/day or less
- Prednisone 10mg/day or less
- Dexamethasone 4mg or less - Note: Recent or current use of inhaled glucocorticoids is not exclusionary, as this route pertains extremely minimal systemic penetration
- Any uncontrolled active medical disorder that would preclude participation as outlined in the opinion of the treating investigator and/or Principal Investigator
- HIV infection
- Subjects who have received or will receive live vaccines within 30 days before the first experimental cell treatment. Inactivated seasonal flu vaccination is allowed
- Subjects with active autoimmune diseases who need systematic treatments (such as disease modifying agents, corticosteroids and immunosuppressive drugs) during the last year Note: Replacement therapy (thyroxine, insulin or physiological corticosteroid replacement therapy (up to10 mg of oral daily prednisone or equivalent in hydrocortisone and dexamethasone) to treat adrenal dysfunction or pituitary dysfunction) is not considered as systematic therapy. Subjects who need inhalation corticosteroid therapy can be included in this trial. Subjects with vitiligo or in long-term remission of pediatric asthma or allergic diseases can be included in this trial
- Subjects with a history of mental disorders or drug abuse that may influence treatment compliance
- Active malignancy not related to CMML that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the Principal Investigator CMML patients who transformed into AML and who were treated back into CMML status are eligible. CMML patients who transformed into AML and appropriate AML treatment was unsuccessful in reverting their disease back to CMML status will be treated as AML patients and are not eligible for the CMML study.
- Treatment with any investigational cell/gene therapy within the past 6 months
- Treatment with any investigational anticancer agent within the last 14 days of study entry or 5 half-lives (whichever is shorter)
- Eligibility for Conditioning Chemotherapy:
- Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values
- Review of co-morbidities to confirm no major changes in health status (examples of major changes include heart attack, stroke, and any major trauma)
- Planned infusion dose was successfully manufactured and met release criteria
- Negative pregnancy testing (if applicable)
- Eligibility for cd4CAR Infusion Inclusion
- Afebrile and not receiving antipyretics, and no evidence of active infection. If fever is attributed to underlying disease, it will not disqualify.
- Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values. The following test does not need repeated: EF if within 6 weeks of initial assessment.
- If previous history of corticosteroid chemotherapy, subject must be off all but adrenal replacement doses 3 days before the CD4CAR infusion
- Note: A subject may still receive the CD4CAR infusion up to 10 days post conditioning chemotherapy as long as they do not meet any of the following at time of infusion:
- Requirement for supplemental oxygen to keep saturation greater than 95% or presence of radiographic abnormalities on a clinically indicated chest x-ray that are progressive.
- New cardiac arrhythmia not controlled with medical management.
- Hypotension requiring pressor support.
- Positive blood cultures for bacteria, fungus, or virus within 48-hours of T cell infusion.
- Contraception and Reproductive Potential Guidelines
- Female subjects of reproductive potential (women who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or have not undergone a sterilization procedure [hysterectomy or bilateral oophorectomy]) must have a negative serum or urine pregnancy test prior to conditioning chemotherapy.
- Due to the high-risk level of this study, while enrolled, all subjects must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization). Additionally, if participating in sexual activity that could lead to pregnancy, the study subject must agree to use reliable and double barrier methods of contraception from time of consent through at least 90 days after CD4CAR infusion.
- Acceptable birth control includes a combination of two of the following methods:
- Condoms (male or female) with or without a spermicidal agent.
- Diaphragm or cervical cap with spermicide
- Intrauterine device (IUD)
- Hormonal-based contraception
- Subjects who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy, salpingotomy, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraception. Acceptable documentation of sterilization, azoospermia, and menopause is specified next:
- Written or oral documentation communicated by clinician or clinician's staff of one of the following:
- Physician report/letter
- Operative report or other source documentation in the subject record (a laboratory report of azoospermia is required to document successful vasectomy)
- Discharge summary
- Laboratory report of azoospermia
- Follicle stimulating hormone measurement elevated into the menopausal range
Trial locations and contacts
4 sites in 1 country.
United States4 sites
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida 33136
Miami, Florida, 33136
Albert Einstein Health Network
The Bronx, New York, 10467
About this study
Official title: CD4CAR T Cell Therapy for CMML
This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-directed chimeric antigen receptor engineered T-cells (CD4CAR) in subjects with relapsed or refractory CMML. Specifically, the study will evaluate the safety and feasibility of CD4CAR T-cells.
Read the detailed description
The study will be performed as a dose-escalation protocol. Due to the relatively low incidence and prevalence of cluster of differentiation 4-positive (CD4+) hematological malignancies and the associated aggressive nature of these diseases and the sequel of treatment failure, the investigators expect to recruit 20 subjects at Indiana University with an expected dropout rate of 25% primarily due to rapid progression or death and screen and or manufacturing failure. Taking this into account, the investigators expect to treat 15 subjects. The study will utilize autologous CD4CAR T-cells that are engineered to express a chimeric antigen receptor (CAR) targeting CD4 that is linked to the cluster of differentiation 28 (CD28), 4-1BB, cluster of differentiation 3-zeta (CD3ζ) signaling chains (third generation CAR).
At entry, disease status will be staged. Qualifying subjects will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for the manufacturing. Next, participants will receive conditioning chemotherapy. If tumor burden is sufficiently reduced (screening step), participants will receive CD4CAR cells by infusion on Day 0 of treatment.
If the disease progresses during the manufacturing period participants may be excluded from the study. Minimal chemotherapy to keep the disease under control in the meanwhile is allowed if deemed necessary by investigators.
A single dose of CD4CAR transduced T cells will consist of the cell number for the dose level to be infused.
Post-infusion monitoring of CD4CAR T-cells: Subjects will have blood drawn for cytokine levels, CD4CAR Transgene Copy Number (PCR) and flow cytometry in order to evaluate the presence of CD4CAR cells on days 0, 1, 3, 5, 7, 14, and 28 following infusion (or as clinically needed). Cytokines levels will be evaluated per schedule above in addition to and as needed every 8 +/- 2 hours as feasible if/when CRS occurs and until resolution. Active monitoring of fungal and viral infections during treatment while utilizing standard prophylaxis recommended for HIV-positive subjects with T-cell aplasia and those undergoing allogeneic stem cell transplant. Investigators plan to collect data about clinicoradiologic measurements of residual tumor burden starting on day 7 and weekly afterward until Day 28 and then monthly for 6 months. This will be followed by quarterly clinical evaluations for the next two (2) years with a medical history, physical examination, and comprehensive blood testing. After these short- and intermediate-term evaluations are performed, these subjects will enter a rollover study to assess for disease-free survival (DFS), relapse, and the development of other health problems or malignancies where follow-up will be up to twice a year by phone and a questionnaire for an additional thirteen (13) years. The treating physician will decide to proceed with allogeneic or autologous transplant when needed.
Dose of CD4CAR description: the main objective of this study is to establish a recommended dose and/or schedule of CD4CAR. The guiding principle for dose escalation in phase I is to avoid unnecessary exposure of subjects to sub-therapeutic doses (i.e., to treat as many subjects as possible within the therapeutic dose range) while preserving safety and maintaining rapid accrual. Investigators will use the rule-based traditional Phase I "3+3" design for the evaluation of safety. Based on lab experience in mice the starting dose (dose level 1) for the first cohort of three subjects in phase I portion of the study will be 8x10^5 cells. The dose escalation or de-escalation will follow a modified Fibonacci sequence as below.
If more than one subject out of the first cohort of three subjects in dose level 1 experience dose limiting toxicity (DLT), the trial will be placed on hold. If zero or one out of three subjects in the first cohort of dose level 1 experience DLT, three more subjects will be enrolled at dose level 1; the dose escalation continues until at least two subjects among a cohort of six subjects experience DLT (i.e., ≥33% of subjects with a DLT at this dose level)
If one of the first three subjects in dose level 1 experiences a DLT, three more subjects will be treated at dose level 1.
If none of the three subjects or only one of the 6 subjects in the dose level 1 experiences a DLT, the dose escalation continues to the dose level 2 If one of the first three subjects in dose level 2 experience a DLT, three more subjects will be treated at dose level 2 If none of the three subjects or only one of the 6 subjects in the dose level2 experiences a DLT, the dose escalation continues to the dose level 3 If one of the first three subjects in dose level 3 experiences a DLT, three more subjects will be treated at dose level 3 If none of the three subjects or only one of the 6 subjects in the dose level 3 experiences a DLT, dose level 3 will be declared the maximum tolerated dose (MTD) and will be used as the recommended phase II dose (RP2D) for the phase II portion of the study.
In summary, the dose escalation continues until at least two subjects among a cohort of six subjects experience DLT (i.e., ≥33% of subjects with a DLT at that dose level). The recommended dose for phase II trials is defined as one dose level below this toxic dose level. Since some grade 3 and possibly 4 toxicities are highly likely to be reversible, grade 3 infectious, hematological and vascular toxicities will not be considered DLTs mandating dose reduction. Also allergic or infusion-related reactions ≤ grade 3 will not be counted as DLTs. There will be no intra-subject dose escalation or reduction.
To allow for full spectrum toxicity duration evaluation and reporting, no subjects within the same or a different cohort will be initiated on lymphodepleting chemotherapy sooner than 28 days from the initiation date of the preceding subject.
- Conditions
- Chronic Myelomonocytic Leukemia
- Being tested
- CD4CAR
- Keywords
- Chronic Myelomonocytic Leukemia, T Cell, Cell Therapy, CAR-T, chimeric antigen
- Medical subject headings
- Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD4CARBiological
CD4CAR cells transduced with a lentiviral vector to express the single-chain variable fragment (scFv) nucleotide sequence of the anti-CD4 molecule derived from humanized monoclonal ibalizumab and the intracellular domains of CD28 and 4-1BB co-activators fused to the CD3ζ T-cell activation signaling domain administered by IV infusions as a single dose
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Redirected autologous T cells transduced with the anti-CD4 lentiviral vector (referred to as "CD4CAR" cells) Receives: Biological: CD4CAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose finding: Maximum tolerated dose (MTD) is defined as one dose level lower than the dose limiting toxicity (DLT) of the CD4CAR in CMML
In this traditional phase 1 dose escalation, cohorts of three subjects will be treated on a dose level that will be incremented to next dose level if no dose limiting toxicities (DLT) were reported or expanded if a DLT is documented
Measured: Day 0 through Day 28 post-infusion
The efficacy of treatment with CD4CAR and description of CMML response to CD4CAR
serial marrow sampling will be analysed for response as measured by reduction on the CMML clonal cells at different time points. Other measures include reduction on transfusion dependency and molecular remissions if at diagnoosis molecular markers were identified.
Measured: Day 28 through 6 months post-infusion
Secondary outcomes (2)
in vivo persistence of a single dose of the CD4CAR in subjects with CMML
Flowcytometry and transgene copy number by PCR will be used to evaluate the CAR T cell persistence post infusion
Measured: Day 0 through Day 28
efficiacy of the CD4CAR to target T regulatory cells and myeloid derived suppressor cells
T regs estimation in marrows will be done at diagnosis and on Day 28 post-infusion. This will be done by flowcytometry to assess the reduction on these cells phenotyped by double positivity for CD4 and FOXP3. At the same time points Myeloid Derived Suppressor Cells (MDSCs), will also be quantified. MDSCs will be identified by a master mix of commercially available antibodies against MDSC subsets including CD16, CD15, CD14, CD45, CD84.etc, Cytek® cFluor® MDSC Ki panel.
Measured: Day 0 through Day 28 post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2023
- Study start21 Feb 2024
- Primary completionDec 2028 (estimated)
- Study completionDec 2043 (estimated)
Why it stopped: Trial being transferred to new lead site
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myelomonocytic LeukemiaStudies of the same condition, open and under way.
- 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huda Salman
- Sponsor type
- University, hospital or other
- Collaborators
- iCell Gene Therapeutics, The Leukemia and Lymphoma Society
- Responsible party
- Sponsor-investigator, Huda Salman, Indiana University
- Investigators
- Huda Salman, MD, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06071624
- Sponsor's protocol ID
- CTO-IUSCCC-0840
- Status last verified
- Sep 2026
- First submitted
- 15 Sep 2023
- Last updated
- 24 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 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD4CAR T Cell Therapy for CMML
- ClinicalTrials.gov ID
- NCT06071624
- Acronym / sponsor ID
- CTO-IUSCCC-0840
- Conditions
- Chronic Myelomonocytic Leukemia
- Keywords
- Chronic Myelomonocytic Leukemia, T Cell, Cell Therapy, CAR-T, chimeric antigen
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Trial being transferred to new lead site
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Huda SalmanUniversity, hospital or other
- Collaborators
- iCell Gene Therapeutics, The Leukemia and Lymphoma Society
- Study start
- 21 Feb 2024 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2043 (estimated)
- First posted
- 6 Oct 2023 (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.
This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-directed chimeric antigen receptor engineered T-cells (CD4CAR) in subjects with relapsed or refractory CMML. Specifically, the study will evaluate the safety and feasibility of CD4CAR T-cells.
Detailed description
The study will be performed as a dose-escalation protocol. Due to the relatively low incidence and prevalence of cluster of differentiation 4-positive (CD4+) hematological malignancies and the associated aggressive nature of these diseases and the sequel of treatment failure, the investigators expect to recruit 20 subjects at Indiana University with an expected dropout rate of 25% primarily due to rapid progression or death and screen and or manufacturing failure. Taking this into account, the investigators expect to treat 15 subjects. The study will utilize autologous CD4CAR T-cells that are engineered to express a chimeric antigen receptor (CAR) targeting CD4 that is linked to the cluster of differentiation 28 (CD28), 4-1BB, cluster of differentiation 3-zeta (CD3ζ) signaling chains (third generation CAR).
At entry, disease status will be staged. Qualifying subjects will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for the manufacturing. Next, participants will receive conditioning chemotherapy. If tumor burden is sufficiently reduced (screening step), participants will receive CD4CAR cells by infusion on Day 0 of treatment.
If the disease progresses during the manufacturing period participants may be excluded from the study. Minimal chemotherapy to keep the disease under control in the meanwhile is allowed if deemed necessary by investigators.
A single dose of CD4CAR transduced T cells will consist of the cell number for the dose level to be infused.
Post-infusion monitoring of CD4CAR T-cells: Subjects will have blood drawn for cytokine levels, CD4CAR Transgene Copy Number (PCR) and flow cytometry in order to evaluate the presence of CD4CAR cells on days 0, 1, 3, 5, 7, 14, and 28 following infusion (or as clinically needed). Cytokines levels will be evaluated per schedule above in addition to and as needed every 8 +/- 2 hours as feasible if/when CRS occurs and until resolution. Active monitoring of fungal and viral infections during treatment while utilizing standard prophylaxis recommended for HIV-positive subjects with T-cell aplasia and those undergoing allogeneic stem cell transplant. Investigators plan to collect data about clinicoradiologic measurements of residual tumor burden starting on day 7 and weekly afterward until Day 28 and then monthly for 6 months. This will be followed by quarterly clinical evaluations for the next two (2) years with a medical history, physical examination, and comprehensive blood testing. After these short- and intermediate-term evaluations are performed, these subjects will enter a rollover study to assess for disease-free survival (DFS), relapse, and the development of other health problems or malignancies where follow-up will be up to twice a year by phone and a questionnaire for an additional thirteen (13) years. The treating physician will decide to proceed with allogeneic or autologous transplant when needed.
Dose of CD4CAR description: the main objective of this study is to establish a recommended dose and/or schedule of CD4CAR. The guiding principle for dose escalation in phase I is to avoid unnecessary exposure of subjects to sub-therapeutic doses (i.e., to treat as many subjects as possible within the therapeutic dose range) while preserving safety and maintaining rapid accrual. Investigators will use the rule-based traditional Phase I "3+3" design for the evaluation of safety. Based on lab experience in mice the starting dose (dose level 1) for the first cohort of three subjects in phase I portion of the study will be 8x10^5 cells. The dose escalation or de-escalation will follow a modified Fibonacci sequence as below.
If more than one subject out of the first cohort of three subjects in dose level 1 experience dose limiting toxicity (DLT), the trial will be placed on hold. If zero or one out of three subjects in the first cohort of dose level 1 experience DLT, three more subjects will be enrolled at dose level 1; the dose escalation continues until at least two subjects among a cohort of six subjects experience DLT (i.e., ≥33% of subjects with a DLT at this dose level)
If one of the first three subjects in dose level 1 experiences a DLT, three more subjects will be treated at dose level 1.
If none of the three subjects or only one of the 6 subjects in the dose level 1 experiences a DLT, the dose escalation continues to the dose level 2 If one of the first three subjects in dose level 2 experience a DLT, three more subjects will be treated at dose level 2 If none of the three subjects or only one of the 6 subjects in the dose level2 experiences a DLT, the dose escalation continues to the dose level 3 If one of the first three subjects in dose level 3 experiences a DLT, three more subjects will be treated at dose level 3 If none of the three subjects or only one of the 6 subjects in the dose level 3 experiences a DLT, dose level 3 will be declared the maximum tolerated dose (MTD) and will be used as the recommended phase II dose (RP2D) for the phase II portion of the study.
In summary, the dose escalation continues until at least two subjects among a cohort of six subjects experience DLT (i.e., ≥33% of subjects with a DLT at that dose level). The recommended dose for phase II trials is defined as one dose level below this toxic dose level. Since some grade 3 and possibly 4 toxicities are highly likely to be reversible, grade 3 infectious, hematological and vascular toxicities will not be considered DLTs mandating dose reduction. Also allergic or infusion-related reactions ≤ grade 3 will not be counted as DLTs. There will be no intra-subject dose escalation or reduction.
To allow for full spectrum toxicity duration evaluation and reporting, no subjects within the same or a different cohort will be initiated on lymphodepleting chemotherapy sooner than 28 days from the initiation date of the preceding subject.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Biological: CD4CARRedirected autologous T cells transduced with the anti-CD4 lentiviral vector (referred to as "CD4CAR" cells) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ≥ 18 years old at the time of informed consent
- Ability to provide written informed consent and HIPAA authorization
- Diagnosis of CMML that is CD4+ and is recurrent or refractory to first line standard of care treatment.
- Creatinine clearance of ≥ 60 ml/min (or otherwise non clinically significant, per study investigator)
- ALT/AST < 3 x ULN
Key exclusion criteria (51 listed)
- CD4 negative CMML
- Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential (see definition below) must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites' clinical policy
- Uncontrolled active infection necessitating systemic therapy
- Active hepatitis B or hepatitis C infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative HCV RNA results exceed the lower detection limit
- Concurrent use of systemic glucocorticoids in greater than replacement doses or steroid dependency defined in rheumatological and pulmonary diseases as uninterrupted corticosteroid intake for more than a year at a dosage of 0.3 mg/kg/day or greater, and where the underlying disease worsens on temporary stoppage of steroid therapy, with symptoms of steroids withdrawal (eg, lethargy, headache, weakness, pseudo rheumatism, emotional disturbances, etc) precipitated by the temporary stoppage unless tapering can occur safely without compromising the underlying disease, the withdrawal tolerance and can happen in a timeframe appropriate to enroll in this trial without safety concerns
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 |
|---|---|---|
| CD4CARCD4CAR cells transduced with a lentiviral vector to express the single-chain variable fragment (scFv) nucleotide sequence of the anti-CD4 molecule derived from humanized monoclonal ibalizumab and the intracellular domains of CD28 and 4-1BB co-activators fused to the CD3ζ T-cell activation signaling domain administered by IV infusions as a single dose | Biological | Treatment |
Primary outcome
Dose finding: Maximum tolerated dose (MTD) is defined as one dose level lower than the dose limiting toxicity (DLT) of the CD4CAR in CMML
Time frame: Day 0 through Day 28 post-infusion
In this traditional phase 1 dose escalation, cohorts of three subjects will be treated on a dose level that will be incremented to next dose level if no dose limiting toxicities (DLT) were reported or expanded if a DLT is documented
The efficacy of treatment with CD4CAR and description of CMML response to CD4CAR
Time frame: Day 28 through 6 months post-infusion
serial marrow sampling will be analysed for response as measured by reduction on the CMML clonal cells at different time points. Other measures include reduction on transfusion dependency and molecular remissions if at diagnoosis molecular markers were identified.
2 secondary outcomes
in vivo persistence of a single dose of the CD4CAR in subjects with CMML
Time frame: Day 0 through Day 28
efficiacy of the CD4CAR to target T regulatory cells and myeloid derived suppressor cells
Time frame: Day 0 through Day 28 post-infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
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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.
Huda Salman, MD, PhD principal investigator
Indiana University
4 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 CD4CAR in people with Chronic Myelomonocytic Leukemia, run by Huda Salman at 4 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 9 inclusion and 51 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: paused, as of the sponsor's last update on 24 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 4 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?
Results are not available in the source record.
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?
Dose finding: Maximum tolerated dose (MTD) is defined as one dose level lower than the dose limiting toxicity (DLT) of the CD4CAR in CMML (time frame: Day 0 through Day 28 post-infusion). The study lists 2 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 24 Sep 2026.