AzTrials
AzTrials

Sickle Cell DiseasePhase 1NCT05384756

TMLI and Alemtuzumab for Treatment of Sickle Cell Disease

A Phase 1 study testing Alemtuzumab, Hematopoietic Cell Transplantation and Intensity-Modulated Radiation Therapy in people with Sickle Cell Disease, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 to 40 yearsHealthy volunteers can take part
Conditions the study is for
Sickle Cell Disease
What is being tested?
Alemtuzumab, Hematopoietic Cell Transplantation and Intensity-Modulated Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
13 Jul 2022to 1 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 12 to 40 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative
  • 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:
Show all 40Show fewer
  • 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

Who cannot join

  • Prior allogeneic or autologous stem cell transplant
  • 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
Show all 15Show fewer
  • 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

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 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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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).

  1. 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.

Being tested
Alemtuzumab, Hematopoietic Cell Transplantation, Intensity-Modulated Radiation Therapy, Sirolimus
Medical subject headings
Anemia, Sickle Cell

What participants receive

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

  • AlemtuzumabDrug

    Also called Anti-CD52 Monoclonal Antibody, Campath, Campath-1H, LDP-03

    Given IV

  • Hematopoietic Cell TransplantationProcedure or surgery

    Also called HCT, Hematopoietic Stem Cell Infusion, Hematopoietic Stem Cell Transplantation, HSCT

    Undergo HCT

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

    Undergo TMLI

  • SirolimusDrug

    Also called AY 22989, RAPA, Rapamune, Rapamycin

    Medication to prevent the development of graft-versus-host disease (GVHD)

Study groups in NCT05384756
Study groupRoleWhat they receive
Treatment (TMLI, alemtuzumab)ExperimentalPatients 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.
Receives: Drug: Alemtuzumab; Procedure: Hematopoietic Cell Transplantation; Radiation: Intensity-Modulated Radiation Therapy; Drug: Sirolimus

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 the Bearman Scale National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients with the unacceptable adverse events will be calculated along with the appropriate Clopper-Pearson 90% confidence intervals.

    Measured: Up to day 100 post-transplant

  2. Feasibility

    Feasibility will be defined as engraftment that would be sufficient to reduce sickle cell disease (SCD) burden (Any donor chimerism with Hgb S =< 30%).

    Measured: Up to 2 years

Secondary outcomes (6)

  1. Platelet engraftment

    Platelet engraftment will be defined as independence from platelet transfusion for at least 7 days with a platelet count of more than >20 × 10^9/L

    Measured: Up to 2 years

  2. Time to acute graft-versus-host disease (grades 2-4 and 3-4) until day +100 after transplant

    Acute Graft versus Host Disease (aGVHD) of grades 2-4 and 3-4: Documented/biopsy proven acute graft versus host disease is graded according to the Consensus Grading. Time to event is measured from date of stem cell infusion to document/biopsy proven acute GVHD onset date (within the first 100 days post-transplant) and will be used to estimate the cumulative incidence.

    Measured: Up to 2 years

  3. Time to chronic graft-versus-host disease for up to one year after transplant

    Chronic Graft versus Host Disease (cGVHD): chronic Graft versus Host Disease (aGVHD) of grades 2-4 and 3-4:

    Documented/biopsy proven chronic graft versus host disease is scored according to NIH Consensus Staging. Time to event is measured from date of stem cell infusion to the documented/biopsy proven chronic GVHD onset date and will be used to estimate the cumulative incidence.

    Measured: Up to 2 years

  4. Overall survival (OS)

    Patients are considered a failure for this endpoint if they die, regardless of cause.

    Measured: From start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 2 years

  5. Event-free survival (EFS)

    Patients are considered a failure for this endpoint if they graft failure, or die, regardless of cause. Time to this event is the time from start of protocol therapy to death, graft failure, or last follow-up, whichever comes first.

    Measured: From start of protocol therapy to death, graft failure, or last follow-up, whichever comes first, assessed up to 2 years

  6. Disease-free Survival (DFS)

    Patients are considered a failure for this endpoint if they die (regardless of cause) or experience disease progression or relapse.

    Measured: From date of stem cell infusion to death, disease relapse/progression, or last follow-up, whichever comes first, assessed 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 posted20 May 2022
  2. Study start13 Jul 2022
  3. Primary completion1 Dec 2026 (estimated)
  4. Study completion1 Dec 2026 (estimated)

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
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05384756
Sponsor's protocol ID
20682
Other IDs
NCI-2022-03571, 20682, P30CA033572
Status last verified
Jul 2026
First submitted
3 May 2022
Last updated
30 Jul 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 Alemtuzumab, Hematopoietic Cell Transplantation and Intensity-Modulated Radiation Therapy in people with Sickle Cell Disease, 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 40 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 30 Jul 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?

This study is still under way. Results are not available in the source record yet.

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: Up to day 100 post-transplant). The study lists 2 primary outcomes in all. 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 NCT05384756.

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 30 Jul 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in