TMLI and Alemtuzumab for Treatment of Sickle Cell Disease

NCT05384756 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 20682NCI-2022-03571P30CA033572
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to day 100 post-transplant

• 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%).

  Up to 2 years

Secondary Outcomes (6)

• Platelet engraftment

  Up to 2 years

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

  Up to 2 years

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

  Up to 2 years

• Overall survival (OS)

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

• Event-free survival (EFS)

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

Other Outcomes (5)

• Immune cell reconstitution

  Up to 2 years

• Quality of life - PedsQL

  Up to 2 years

• Bone marrow environment inflation - levels of inflammatory cytokines

  Baseline only (pre-conditioning)

Study Arms (1)

Treatment (TMLI, alemtuzumab)

EXPERIMENTAL

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.

Drug: Alemtuzumab; Procedure: Hematopoietic Cell Transplantation; Radiation: Intensity-Modulated Radiation Therapy; Drug: Sirolimus

Interventions

Alemtuzumab DRUG

Given IV

Also known as: Anti-CD52 Monoclonal Antibody, Campath, Campath-1H, LDP-03, Lemtrada, MabCampath, Monoclonal Antibody Campath-1H

Treatment (TMLI, alemtuzumab)

Hematopoietic Cell Transplantation PROCEDURE

Undergo HCT

Also known as: HCT, Hematopoietic Stem Cell Infusion, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation

Treatment (TMLI, alemtuzumab)

Intensity-Modulated Radiation Therapy RADIATION

Undergo TMLI

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Treatment (TMLI, alemtuzumab)

Sirolimus DRUG

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

Also known as: AY 22989, RAPA, Rapamune, Rapamycin, SILA 9268A, WY-090217

Treatment (TMLI, alemtuzumab)

Eligibility Criteria

• Age: 12 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Alemtuzumab; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Radiotherapy, Intensity-Modulated; Sirolimus

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Macrolides; Lactones; Organic Chemicals

Study Officials

• Anna Pawlowska

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: May 20, 2022
• Study Start: July 13, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 5, 2026

Record last verified: 2025-12

Locations

US (1)