Trials / Recruiting
RecruitingNCT06195891
Orca-T Following Chemotherapy and Total Marrow and Lymphoid Irradiation for the Treatment of Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome
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
- Status
- Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 33 (estimated)
- Sponsor
- City of Hope Medical Center · Academic / Other
- Sex
- All
- Age
- 60 Years
- Healthy volunteers
- Accepted
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 (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.
Detailed description
PRIMARY OBJECTIVES: I. 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: I. 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: I. 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. V. 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.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | Biospecimen Collection | Undergo blood sample collection |
| PROCEDURE | Bone Marrow Aspiration | Undergo bone marrow aspiration |
| PROCEDURE | Bone Marrow Biopsy | Undergo bone marrow biopsy |
| PROCEDURE | Dual-Energy Computed Tomography | Undergo DECT/MRI scan |
| PROCEDURE | Echocardiography | Undergo echocardiography |
| DRUG | Fludarabine | Given IV |
| PROCEDURE | Magnetic Resonance Imaging | Undergo DECT/MRI scan |
| DRUG | Melphalan | Given IV |
| PROCEDURE | Multigated Acquisition Scan | Undergo MUGA scan |
| BIOLOGICAL | Partially Engineered T-regulatory Cell Donor Graft TRGFT-201 | Given IV |
| DRUG | Tacrolimus | Given tacrolimus |
| DRUG | Thiotepa | Given IV |
| RADIATION | Total Marrow and Lymphoid Irradiation | Undergo TMLI |
Timeline
- Start date
- 2024-05-24
- Primary completion
- 2027-06-21
- Completion
- 2027-06-21
- First posted
- 2024-01-08
- Last updated
- 2025-11-10
Locations
1 site across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT06195891. Inclusion in this directory is not an endorsement.