Ignite Creation Date:
2024-05-06 @ 7:56 PM
Last Modification Date:
2024-10-26 @ 3:17 PM
Study NCT ID:
NCT06195891
Status:
RECRUITING
Last Update Posted:
2024-05-23
First Post:
2023-12-05
Brief Title:
Orca-T Following Chemotherapy and Total Marrow and Lymphoid Irradiation for the Treatment of Acute Myeloid Leukemia Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome
Sponsor:
City of Hope Medical Center
Organization:
City of Hope Medical Center
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 patients 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 relapseprogression 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 onsetresolution
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 CD34hematopoietic 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 physicians discretion
Patients also undergo echocardiogram ECHO or multigated acquisition MUGA scans dual energy computed tomography DECTmagnetic resonance imaging MRI scans bone marrow biopsiesaspirates and blood sample collection throughout the study
After completion of study treatment patients are followed for up to 2 years from enrollment
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 relapseprogression 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 onsetresolution
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 CD34hematopoietic 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 physicians discretion
Patients also undergo echocardiogram ECHO or multigated acquisition MUGA scans dual energy computed tomography DECTmagnetic resonance imaging MRI scans bone marrow biopsiesaspirates and blood sample collection throughout the study
After completion of study treatment patients are followed for up to 2 years from enrollment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2023-08816 | REGISTRY | None | None |
| 23343 | OTHER | None | None |
| P30CA033572 | NIH | City of Hope Medical Center | httpsreporternihgovquickSearchP30CA033572 |