ACTIVE_NOT_RECRUITING

TMLI and Alemtuzumab for Treatment of Sickle Cell Disease

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Conditions

Sickle Cell Disease

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2022-07-13
Study Completion:2026-12-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05384756

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 40 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:Yes
Standard Ages:CHILD, ADULT
Inclusion CriteriaExclusion Criteria
  1. * Documented informed consent of the participant and/or legally authorized representative
  2. * Assent, when appropriate, will be obtained per institutional guidelines
  3. * Registered into Risk Evaluation and Mitigation Strategies (REMS) program
  4. * Age: 12-40 years
  5. * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
  6. * 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:
  7. * Significant neurologic event (stroke) or any neurological deficit lasting \> 24 hours; or increased transcranial Doppler velocity (\> 200 m/s).
  8. * 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).
  9. * 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).
  10. * Recurrent priapism requiring medical therapy.
  11. * Osteonecrosis of two or more joints despite the institution of supportive care measures.
  12. * 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)
  13. * Echocardiograph finding of tricuspid valve regurgitation jet (TRJ) velocity \>= 2.5 m/sec.
  14. * Have a related donor who is matched on at least 8/10 human leukocyte antigen (HLA)-A, B, C, and DRB1 Loci
  15. * Total bilirubin =\< 2.5 x upper limit normal (ULN( (unless has Gilbert's disease) (performed within 30 days prior to day 1 of protocol)
  16. * Aspartate aminotransferase (AST) =\< 1.5 x ULN (performed within 30 days prior to day 1 of protocol)
  17. * Alanine aminotransferase (ALT) =\< 1.5 x ULN (performed within 30 days prior to day 1 of protocol)
  18. * 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)
  19. * 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)
  20. * If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
  21. * If not receiving anticoagulants: Activated Partial Thromboplastin Time (aPTT) =\<1.5 x ULN (performed within 30 days prior to day 1 of protocol)
  22. * If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
  23. * Left ventricular ejection fraction (LVEF) \>= 50% (performed within 30 days prior to day 1 of protocol)
  24. * Note: To be performed within 28 days prior to Day 1 of protocol therapy.
  25. * 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)
  26. * If unable to perform pulmonary function tests: Oxygen (O 2) saturation \> 92% on room air
  27. * Note: To be performed within 28 days prior to Day 1 of protocol therapy.
  28. * 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 \[RPR\])
  29. * If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
  30. * Meets other institutional and federal requirements for infectious disease titer requirements
  31. * Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
  32. * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
  33. * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be require.
  34. * 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.
  35. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  36. * DONOR: Age =\< 60 years
  37. * DONOR: Medical history and physical examination confirm good health status as defined by institutional standards
  38. * 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)
  39. * 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.
  40. * 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
  1. * Prior allogeneic or autologous stem cell transplant
  2. * Patients who are receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
  3. * History of allergic reactions attributable to compounds of similar chemical or biologic composition to study agent
  4. * Patients with any active malignancy are ineligible for this study, other than non-melanoma skin cancers
  5. * 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.
  6. * Active infection requiring antibiotics
  7. * Females only: Pregnant or breastfeeding
  8. * 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
  9. * 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)
  10. * DONOR: Evidence of active infection
  11. * 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
  12. * 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
  13. * DONOR: Lactating female or, if of child-bearing potential, is unwilling to implement adequate birth control
  14. * DONOR: HIV positive
  15. * DONOR: Prior radiation therapy

Contacts and Locations

Principal Investigator

Anna Pawlowska
PRINCIPAL_INVESTIGATOR
City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center
Duarte, California, 91010
United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

  • Anna Pawlowska, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-13
Study Completion Date2026-12-01

Study Record Updates

Study Start Date2022-07-13
Study Completion Date2026-12-01

Terms related to this study

Additional Relevant MeSH Terms

  • Sickle Cell Disease