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Acute Lymphoblastic LeukemiaPhase 1NCT06195891

Orca-T Following Chemotherapy and Total Marrow and Lymphoid Irradiation for the Treatment of Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome

A Phase 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

This phase I trial tests the side effects and best dose of total marrow lymphoid irradiation along with chemotherapy, with fludarabine and melphalan, with or without thiotepa, in combination with Orca-T cells for patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome… Read more about this study

Who is it for?
Ages 60 years and olderHealthy volunteers can take part
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
1 siteUnited States
Study dates
24 May 2024to 22 Mar 2030
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 60 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant
  • Agreement to allow the use of archival tissue from diagnostic bone marrow biopsies
  • If unavailable, exceptions may be granted with study primary investigator (PI) approval
  • Age: 60-75 years
  • Karnofsky performance status ≥ 70
  • Eligible patients will have a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories:
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  • Acute myelogenous leukemia:
  • Patients with de novo or secondary disease in CR1 or more with European LeukemiaNet (ELN) intermediate or adverse risk category, or
  • Patients with active disease
  • Morphologically; or
  • Minimal residual disease (MRD) + (flow cytometry of ≥ 0.1%, next generation sequencing [NGS] or cytogenetics)
  • Acute lymphoblastic leukemia (ALL):
  • Patients with de novo or secondary disease according to National Comprehensive Cancer Network (NCCN) guidelines for ALL hypoploidy (< 44 chromosomes); t(v;11q23): MLL rearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (≥ 30,000 for B lineage or ≥ 50,000 for T lineage); iAMP21loss of 13q, and abnormal 17p; or
  • Patients with active disease:
  • Morphologically; or
  • MRD+ (flow cytometry of ≥ 0.1%, or cytogenetics)
  • Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories per International Prognostic Scoring System Risk (IPSSR)
  • Serum direct (conjugated) bilirubin ≤ 2.0 mg/dl performed within 30 days prior to day 1
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 times the institutional upper limits of normal performed within 30 days prior to day 1. Patients with Gilberts disease are allowed
  • Creatinine clearance of ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula performed within 30 days prior to day 1
  • Ejection fraction measured by echocardiogram or MUGA ≥ 50% performed within 30 days prior to day 1
  • If able to perform pulmonary function tests: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capability (DLCO) (diffusion capacity) ≥ 50% of predicted (corrected for hemoglobin).
  • If unable to perform pulmonary function tests: oxygen (O2) saturation > 92% on room air performed within 30 days prior to day 1
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test performed within 30 days prior to day 1. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy.
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
  • PATIENTS: Patients should have discontinued all previous intensive therapy, chemotherapy or radiotherapy for 2 weeks prior to commencing therapy on this study NOTE: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors (TKIs). FLT-3 inhibitors can also be given up to 3 days before conditioning regimen.) All patients with prior radiation treatment to the lung, liver, and kidney will be excluded. For other scenarios of prior radiation treatment, up to 2000 cGy at 2 Gy per day will be allowed. Inclusion of patients with previous radiation exposure will be determined based on the radiation oncologist medical doctor (MD) evaluation and judgment
  • DONORS: All candidates for this study must have an human leukocyte antigen (HLA) (A, B, C, and DR) identical sibling who is willing to donate mobilized peripheral blood stem cells or have a 10/10 (A, B, C, DR and DQ) allele matched unrelated donor (DQ or DP mismatch is allowed per discretion of the principal investigator), or haploidentical donor. City of Hope (COH) standard operating procedures (SOP) (B.001.11) will be used for allogeneic donor evaluation, selection, and consent. Donor screening will be in compliance with all requirements of Food and Drug Administration (FDA) regulation 21 Code of Federal Regulations (CFR) Part 1271 including donor screening for COVID-19 exposure or infection

Who cannot join

  • PATIENTS: Prior allogeneic stem cell transplant
  • PATIENTS: More than 3 prior lines of intensive chemotherapy, where the regimen intent was to induce remission
  • PATIENTS: Receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous 2 weeks from conditioning NOTE: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include: Hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors (TKIs). FLT-3 inhibitors can also be given up to 3 days before conditioning regimen
  • PATIENTS: History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  • PATIENTS: Having any uncontrolled illness including ongoing or active bacterial, viral or fungal infection requiring antibiotics
  • PATIENTS: Patients with other active malignancies are ineligible for this study, other than non-melanoma skin cancer, in situ cervical cancer and prostate cancer. Patients with prior history of localized prostate cancer treated with curative intent regardless of time from the treatment to study entry, and patients with prostate cancer receiving active surveillance not requiring therapy are eligible
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  • PATIENTS: The recipient has a medical problem or neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery which in the opinion of the principal investigator would place the recipient at unacceptable risk
  • PATIENTS: Females only: Pregnant or breastfeeding
  • PATIENTS: Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • PATIENTS: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Single Center, Non-Randomized, Phase 1b Study of Orca-T Following Escalated Dose of Total Marrow and Lymphoid Irradiation in Patients With Acute Leukemias and MDS

This phase I trial tests the side effects and best dose of total marrow lymphoid irradiation along with chemotherapy, with fludarabine and melphalan, with or without thiotepa, in combination with Orca-T cells for patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS). Total marrow and lymphoid irradiation is a targeted form of total body irradiation that uses intensity-modulated radiation therapy to target marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize the radiation therapeutic effect. Giving chemotherapy with medications such as thiotepa, fludarabine, and melphalan before a treatment with stem cells helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Orca-T cells take cells from a donor and remove some of the T cells and replace them with partially engineered T cells in order to induce better tolerance in patients. Giving total marrow and lymphoid irradiation and chemotherapy followed by Orca -T cells may be an effective treatment for patients with AML, ALL or MDS.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Describe toxicities attributable to total marrow and lymphoid irradiation (TMLI) by dose level in patients with high-risk acute leukemias or MDS, in the context of partially engineered T-regulatory cell donor graft TRGFT-201 (Orca-T) from a matched or haploidentical donor.

II. Determine the recommended phase II dose (RP2D) of TMLI with an Orca-T for allogeneic hematopoietic cell transplantation (HCT).

SECONDARY OBJECTIVES:

  1. Determine incidence of acute and late HCT-related immune complications (infections, etc.) at 100 days and 1 year.

II. To evaluate the safety of the regimen, at each dose level, by assessing the following: type, frequency, severity, attribution, time course and duration of adverse events in dose limiting toxicity (DLT) window of 28 days at each dose level, including acute graft-versus-host disease (GVHD), infection and delayed engraftment within the first 100 days and chronic GVHD incidence at 1 year.

III. Measure incidence of acute and chronic GVHD at 100 days and 1-year post-HCT, respectively.

IV. Measure GVHD-free and relapse-free survival (GRFS) at 1-year post-HCT.

EXPLORATORY OBJECTIVES:

  1. Estimate overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100 days, 1 year and 2 years.

II. Evaluate the effect of TMLI as conditioning for Orca-T HCT on immune reconstitution at 1, 3, 6, 9 and 12 months after alloHCT.

III. Evaluate GVHD biomarkers and inflammatory cytokines on days +7, +14, and +30, (all patients) and upon GVHD onset/resolution.

IV. Investigate the temporal effect and bone marrow residual damage and regeneration on days +30, +100, and 1-year post-alloHCT by using longitudinally collected biological samples and imaging.

  1. Monitor effects of TMLI as conditioning on gastrointestinal (GI) toxicity and T cell signaling pathways.

VI. Monitor effects of TMLI on GI microbiome diversity.

OUTLINE: This is a dose-escalation study of TMLI followed by a dose-expansion study.

PREPARATIVE REGIMEN: Patients undergo TMLI twice a day (BID) on days -8 to -5, followed by fludarabine intravenously (IV) on days -4 to -2 and melphalan IV on day -2. Patients receiving the lowest dose of TMLI also receive thiotepa IV on days -4 and -3.

HCT: Patients receive Orca-T CD34+hematopoietic stem and progenitor cells (HSPC) and T-regulatory cell (Treg) products IV on day 0, followed by the Orca-T conventional t-cell (tcon) product IV on day 2.

GVHD PROPHYLAXIS: Patients undergoing haploidentical (haplo)-HCT receive tacrolimus starting on day 14 and continuing until day 90 with a taper per treating physician's discretion.

Patients also undergo echocardiogram (ECHO) or multigated acquisition (MUGA) scans, dual energy computed tomography (DECT)/magnetic resonance imaging (MRI) scans, bone marrow biopsies/aspirates, and blood sample collection throughout the study.

After completion of study treatment, patients are followed for up to 2 years from enrollment.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Dual-Energy Computed Tomography, Echocardiography
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Dual-Energy Computed TomographyProcedure or surgery

    Also called DECT

    Undergo DECT/MRI scan

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo echocardiography

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo DECT/MRI scan

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA scan

  • Partially Engineered T-regulatory Cell Donor Graft TRGFT-201Biological

    Also called Orca-T, Partially Engineered and Enriched Treg Donor Graft TRGFT-201, T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells, TregGraft

    Given IV

  • TacrolimusDrug

    Also called FK 506, FK-506, Fujimycin, Hecoria

    Given tacrolimus

  • ThiotepaDrug

    Also called 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa

    Given IV

  • Total Marrow and Lymphoid IrradiationRadiation

    Also called TMLI

    Undergo TMLI

Study groups in NCT06195891
Study groupRoleWhat they receive
Treatment (TMLI, fludarabine, melphalan, Orca-T)ExperimentalPREPARATIVE REGIMEN: Patients undergo TMLI BID on days -8 to -5, followed by fludarabine IV on days -4 to -2 and melphalan IV on day -2. Patients receiving the lowest dose of TMLI also receive thiotepa IV on days -4 and -3. HCT: Patients receive Orca-T CD34+HSPC and Treg products IV on day 0, followed by the Orca-T tcon product IV on day 2. GVHD PROPHYLAXIS: Patients undergoing haplo-HCT receive tacrolimus starting on day 14 and continuing until day 90 with a taper per treating physician's discretion. Patients also undergo ECHO or MUGA scans, DECT/MRI scans, bone marrow biopsies/aspirates, and blood sample collection throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Dual-Energy Computed Tomography; Procedure: Echocardiography; Drug: Fludarabine; Procedure: Magnetic Resonance Imaging; Drug: Melphalan; Procedure: Multigated Acquisition Scan; Biological: Partially Engineered T-regulatory Cell Donor Graft TRGFT-201; Drug: Tacrolimus; Drug: Thiotepa; Radiation: Total Marrow and Lymphoid Irradiation

What is being measured

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

  1. Incidence of adverse events

    Will be scored on both the Bearman Scale and National Cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 scale.

    Measured: From start of conditioning to day +100

Secondary outcomes (6)

  1. Relapse/progression rate

    The event is relapse/progression. Time to this event is measured from start of therapy. Death without relapse/progression is considered a competing risk. Surviving patients with no history of relapse/progression are censored at time of last follow-up.

    Measured: From start of therapy to relapse/progression, up to 2 years

  2. Non-relapse mortality

    Will be calculated using the Kaplan-Meier method.

    Measured: From start of therapy until non-disease related death, disease relapse/progression, whichever comes first, up to 2 years

  3. Incidence of infection

    Will be reported by site of disease, date of onset, severity and resolution, if any.

    Measured: From day 0 to day +100

  4. Incidence of adverse events

    Toxicities of grade 3, 4, or 5 per Bearman Scale and CTCAE v5.0.

    Measured: From day -9 to day +100

  5. Acute graft versus host disease (GVHD) of grades 2-4 and 3-4

    Documented/biopsy proven acute graft versus host disease is graded according to the 2016 consensus grading.

    Measured: From date of stem cell infusion to document/biopsy proven acute GVHD onset date (within the first 100 days post-transplant)

  6. Chronic Graft versus Host Disease rate

    Documented/biopsy proven chronic graft versus host disease (cGvHD) is scored. Time to event is measured from approximately 80-100 days post-transplant to the documented/biopsy proven chronic GVHD onset date and will be used to estimate the cumulative incidence. Relapse/NRM will be competing risk events for cGVHD.

    Measured: From approximately 80-100 days post-transplant to the documented/biopsy proven chronic GVHD, up to 2 years

Timeline

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

  1. First posted8 Jan 2024
  2. Study start24 May 2024
  3. Primary completion22 Mar 2030 (estimated)
  4. Study completion22 Mar 2030 (estimated)

Why it stopped: Timeline Adjustment

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06195891
Sponsor's protocol ID
23343
Other IDs
NCI-2023-08816, 23343, P30CA033572
Status last verified
Oct 2026
First submitted
5 Dec 2023
Last updated
15 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 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by City of Hope Medical 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 28 inclusion and 10 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 15 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 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?

Incidence of adverse events (time frame: From start of conditioning to day +100). 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 NCT06195891.

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 15 Oct 2026.

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