TMLI and Alemtuzumab for Treatment of Sickle Cell Disease
NCT ID: NCT05384756
Last Updated: 2024-12-31
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1
20 participants
INTERVENTIONAL
2022-07-13
2026-12-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment (TMLI, alemtuzumab)
Patients receive alemtuzumab IV over 4 hours QD on days -7 to -3. Patients undergo TMLI BID on day -2. Patients also undergo HCT on day 0 and receive sirolimus on day -1 and day 0.
Alemtuzumab
Given IV
Hematopoietic Cell Transplantation
Undergo HCT
Intensity-Modulated Radiation Therapy
Undergo TMLI
Sirolimus
Medication to prevent the development of graft-versus-host disease (GVHD)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Alemtuzumab
Given IV
Hematopoietic Cell Transplantation
Undergo HCT
Intensity-Modulated Radiation Therapy
Undergo TMLI
Sirolimus
Medication to prevent the development of graft-versus-host disease (GVHD)
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Assent, when appropriate, will be obtained per institutional guidelines
* Registered into Risk Evaluation and Mitigation Strategies (REMS) program
* Age: 12-40 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Have a diagnosis of sickle cell disease, be at a high risk for disease related morbidity or mortality, which must be defined by one of the following disease status criteria:
* Significant neurologic event (stroke) or any neurological deficit lasting \> 24 hours; or increased transcranial Doppler velocity (\> 200 m/s).
* History of one or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea).
* History of one or more severe vaso-occlusive pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea).
* Recurrent priapism requiring medical therapy.
* Osteonecrosis of two or more joints despite the institution of supportive care measures.
* Prior treatment with regular red blood cell (RBC) transfusion therapy, defined as receiving 8 or more transfusions per year for \> 1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
* Echocardiograph finding of tricuspid valve regurgitation jet (TRJ) velocity \>= 2.5 m/sec.
* Have a related donor who is matched on at least 8/10 human leukocyte antigen (HLA)-A, B, C, and DRB1 Loci
* Total bilirubin =\< 2.5 x upper limit normal (ULN( (unless has Gilbert's disease) (performed within 30 days prior to day 1 of protocol)
* Aspartate aminotransferase (AST) =\< 1.5 x ULN (performed within 30 days prior to day 1 of protocol)
* Alanine aminotransferase (ALT) =\< 1.5 x ULN (performed within 30 days prior to day 1 of protocol)
* Creatinine clearance (CrCl) of \>= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (performed within 30 days prior to day 1 of protocol)
* If not receiving anticoagulants: International Normalized Ratio (INR) OR Prothrombin (PT) =\< 1.5 x ULN (performed within 30 days prior to day 1 of protocol)
* If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
* If not receiving anticoagulants: Activated Partial Thromboplastin Time (aPTT) =\<1.5 x ULN (performed within 30 days prior to day 1 of protocol)
* If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
* Left ventricular ejection fraction (LVEF) \>= 50% (performed within 30 days prior to day 1 of protocol)
* Note: To be performed within 28 days prior to Day 1 of protocol therapy.
* If able to perform pulmonary function tests: Forced expiratory volume in 1 second (FEV1), force vital capacity (FVC), and diffused lung capacity of carbon monoxide (DLCO) (diffusion capacity) \>= 50% of predicted (corrected for hemoglobin)
* If unable to perform pulmonary function tests: Oxygen (O 2) saturation \> 92% on room air
* Note: To be performed within 28 days prior to Day 1 of protocol therapy.
* Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma regain \[RPR\])
* If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
* Meets other institutional and federal requirements for infectious disease titer requirements
* Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be require.
* 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 Six 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)
* DONOR: Age =\< 60 years
* DONOR: Medical history and physical examination confirm good health status as defined by institutional standards
* DONOR: Serologies for: Hepatitis B (HBV) Core Antibody, HIV I/II Antibody, human T-lymphotropic virus (HTLV) - I/II antibody, HCV antibody, Hepatitis B surface antigen, Serologic Test for Syphilis, HIV-1/HCV/HBV nucleic acid, West Nile virus nucleic acid, Trypanosoma cruzi antibody, Cytomegalovirus (CMV) antibody, (AKA: Donor Room Serologies)
* DONOR: Female donors of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (b-HCG) test within 30 days of initiation of conditioning, 30 days of patients admission for conditioning and 7 days of mobilization or bone marrow harvest.
* DONOR: The donor must be informed of the investigational nature of this study and have signed a consent form in accordance with Federal Guidelines and the guidelines of the participating institution
Exclusion Criteria
* Patients who are receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
* History of allergic reactions attributable to compounds of similar chemical or biologic composition to study agent
* Patients with any active malignancy are ineligible for this study, other than non-melanoma skin cancers
* Medical problem or neurologic/psychiatric dysfunction which would impair patient 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.
* Active infection requiring antibiotics
* Females only: Pregnant or breastfeeding
* 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
* 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)
* DONOR: Evidence of active infection
* DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis if donating peripheral stem cells or unlikely to tolerate general anesthesia and bone marrow collection if donating a bone marrow
* DONOR: Factors which place the donor at increased risk for complications from leukapheresis or granulocyte colony-stimulating Factor (G-CSF) therapy if donating peripheral stem cells or general anesthesia and bone marrow collection if donating a bone marrow
* DONOR: Lactating female or, if of child-bearing potential, is unwilling to implement adequate birth control
* DONOR: HIV positive
* DONOR: Prior radiation therapy
12 Years
40 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
City of Hope Medical Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Anna Pawlowska
Role: PRINCIPAL_INVESTIGATOR
City of Hope Medical Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
City of Hope Medical Center
Duarte, California, United States
Countries
Review the countries where the study has at least one active or historical site.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Anna Pawlowska
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2022-03571
Identifier Type: REGISTRY
Identifier Source: secondary_id
20682
Identifier Type: OTHER
Identifier Source: secondary_id
20682
Identifier Type: -
Identifier Source: org_study_id