Ignite Creation Date:
2025-12-24 @ 11:24 PM
Ignite Modification Date:
2025-12-25 @ 9:09 PM
Study NCT ID:
NCT05384756
Status:
RECRUITING
Last Update Posted:
2024-12-31
First Post:
2022-05-03
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
TMLI and Alemtuzumab for Treatment of Sickle Cell Disease
Sponsor:
City of Hope Medical Center
Organization:
Study Overview
Official Title:
A Pilot Study of Nonmyeloablative Regimen Using Total Marrow and Lymphoid Irradiation for Irradiation Sparing of Bystander Organs in Hematopoietic Cell Transplantation From Matched Related or Unrelated Donor in Patients With Sickle Cell Disease
Status:
RECRUITING
Status Verified Date:
2024-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial tests the safety and effectiveness of total marrow and lymphoid irradiation (TMLI) and alemtuzumab as a conditioning regimen in patients with sickle cell disease. Conditioning regimens are treatments used to prepare a patient for stem cell transplantation. A stem cell transplant is a procedure in which a person receives blood stem cells, which make any type of blood cell. A conditioning regimen may include chemotherapy, monoclonal antibody therapy, and radiation to the entire body. It helps make room in the patient's bone marrow for new blood stem cells to grow, and helps prevent the patient's body from rejecting the transplanted cells. Alemtuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Graft-versus-host disease (GVHD) is a complication that may occur after hematopoietic cell transplantation (HCT) in which donated cells view the recipient's cells as foreign and attack them. Giving TMLI and alemtuzumab may help reduce organ damage that can be caused by radiation and decrease the risk of GVHD.
Detailed Description:
PRIMARY OBJECTIVE:
I. Evaluate the safety and feasibility of a fixed TMLI dose of 600 cGy with alemtuzumab as non-myeloablative conditioning (NMC) regimen in patients with sickle cell disease to achieve stable engraftment by Day +100 post HCT.
SECONDARY OBJECTIVES:
I. Assess the hematopoietic recovery by determining donor neutrophil engraftment, platelet engraftment.
II. Assess irradiation doses to non-target organs (lungs, heart, liver, spleen, kidneys, and gonads).
III. Assess the incidence of acute GvHD (grade II - IV) during the first 100 days after transplantation and chronic GvHD at 1 year post-HCT.
IV. Assess overall, event-free, and disease free survival at 1 year post-HCT. V. Assess donor chimerism at day +100 and 1 and 2 years after HCT.
EXPLORATORY OBJECTIVES:
I. Assess immune reconstitution post HCT on baseline, then on days +15, +30, +60, and +180, and 1-year post-HCT. II. Assessment of quality of life at baseline, Day+100, Day +180 and at 1-year post-HCT.
III. Define the impact of sickle cell disease (SCD) including inflammation on the bone marrow microenvironment and hematopoietic cells function at baseline.
IV. Monitor treatment response noninvasively on the recovery of bone marrow microenvironment (hematopoietic and vascular).
V. Monitor treatment response noninvasively on cerebral blood flow (CBF).
OUTLINE:
Patients receive alemtuzumab intravenously (IV) over 4 hours once daily (QD) on days -7 to -3. Patients undergo TMLI twice daily (BID) on day -2. Patients also undergo HCT on day 0 and receive sirolimus on day -1 and day 0.
After study treatment, patients are followed up on day 30, and for up to 2 years.
I. Evaluate the safety and feasibility of a fixed TMLI dose of 600 cGy with alemtuzumab as non-myeloablative conditioning (NMC) regimen in patients with sickle cell disease to achieve stable engraftment by Day +100 post HCT.
SECONDARY OBJECTIVES:
I. Assess the hematopoietic recovery by determining donor neutrophil engraftment, platelet engraftment.
II. Assess irradiation doses to non-target organs (lungs, heart, liver, spleen, kidneys, and gonads).
III. Assess the incidence of acute GvHD (grade II - IV) during the first 100 days after transplantation and chronic GvHD at 1 year post-HCT.
IV. Assess overall, event-free, and disease free survival at 1 year post-HCT. V. Assess donor chimerism at day +100 and 1 and 2 years after HCT.
EXPLORATORY OBJECTIVES:
I. Assess immune reconstitution post HCT on baseline, then on days +15, +30, +60, and +180, and 1-year post-HCT. II. Assessment of quality of life at baseline, Day+100, Day +180 and at 1-year post-HCT.
III. Define the impact of sickle cell disease (SCD) including inflammation on the bone marrow microenvironment and hematopoietic cells function at baseline.
IV. Monitor treatment response noninvasively on the recovery of bone marrow microenvironment (hematopoietic and vascular).
V. Monitor treatment response noninvasively on cerebral blood flow (CBF).
OUTLINE:
Patients receive alemtuzumab intravenously (IV) over 4 hours once daily (QD) on days -7 to -3. Patients undergo TMLI twice daily (BID) on day -2. Patients also undergo HCT on day 0 and receive sirolimus on day -1 and day 0.
After study treatment, patients are followed up on day 30, and for up to 2 years.
Study Oversight
Has Oversight DMC:
True
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2022-03571 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 20682 | OTHER | City of Hope Medical Center | View | |
| P30CA033572 | NIH | None | https://reporter.nih.gov/quic… | View |