RECRUITING

Sickle Cell Disease Transplant Using a Nonmyeloablative Approach for Patients With Anti-donor Red Cell AntibodY

Conditions

Sickle Cell Disease ABO Mismatch SUN-RAY Matched Sibling Donor (MSD)

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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 multicenter prospective study seeks to determine if daratumumab given, prior to HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus, can prevent pure red blood cell aplasia with an acceptable safety profile in patients with anti-donor red blood cell antibodies, achieving an event-free survival similar to transplanted patients without such antibodies.

Official Title

Sickle Cell Disease Transplant Using a Nonmyeloablative Approach: Adding Daratumumab for Patients With Anti-donor Red Cell AntibodY

Quick Facts

Study Start:2024-04-03

Study Completion:2054-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06358638

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:2 Years to 25 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Patients with SCD age 2-24.99 years who have a healthy HLA-identical sibling donor with major ABO incompatibility OR patients with RBC alloantibodies against other donor RBC antigens. * Patients must have an absolute neutrophil count of 1 x 109/L and a platelet count of 100 x 109/L. * Lansky/Karnofsky score of, at least, 70. * History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥200 cm/sec by the non-imaging technique measured at a minimum of two separate occasions. * Progression of CNS vasculopathy on MRA determined to be secondary to SCD. * History of cerebral infarction on brain MRI (overt stroke, or silent stroke if ≥3 mm in one dimension, visible in two planes on fluid-attenuated inversion recovery T2-weighted images). * History of two or more episodes of Acute Chest Syndrome (ACS) in lifetime. * History of three or more SCD pain events requiring treatment with an opiate or IV pain medication in lifetime. * History of any hospitalization for a complication secondary to SCD (does NOT include empiric hospitalizations for fever only). * History of two or more episodes of priapism. * Administration of regular RBC transfusions (≥8 transfusions episodes in the previous 12 months). * At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration. * Clinically significant neurologic event (overt stroke). * History of two or more episodes of ACS in the 2-year period preceding enrollment. * History of three or more SCD pain events requiring treatment with an opiate or IV pain medication (inpatient or outpatient) in the 1-year period preceding enrollment. * History of any hospitalization for SCD pain or ACS while receiving hydroxyurea treatment. * History of two or more episodes of priapism (erection lasting ≥4 hours or requiring emergent medical care). * Administration of regular RBC transfusions (≥8 transfusions in the previous 12 months) * At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.	* Life expectancy less than 6 month * Pregnant or breastfeeding patients. * Infectious Disease: Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning. Patients with confirmed seropositivity for HIV and patients with active or resolved Hepatitis B or C determined by serology and/or NAAT are excluded. * Liver: Direct (conjugated) bilirubin \> 1.5 mg/dL. Transaminases \>5x upper limit of normal for age. * Cardiac: Left ventricular shortening fraction \<25% or ejection fraction \<50% by ECHO. Uncontrolled cardiac arrhythmia. * Kidney: Estimated creatinine clearance less than 60 mL/min/1.73m2. * Pulmonary function: Diffusion capacity of carbon monoxide (DLCO) \<35% (adjusted for hemoglobin). Baseline oxygen saturation \<94% at rest or PaO2 \<70. Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. * Heme: Available, medically suitable, and equivalent HLA-matched sibling donor, who does not have major ABO incompatibility or express RBC antigens against which the patient is alloimmunized.

Inclusion Criteria

Exclusion Criteria

* Patients with SCD age 2-24.99 years who have a healthy HLA-identical sibling donor with major ABO incompatibility OR patients with RBC alloantibodies against other donor RBC antigens.
* Patients must have an absolute neutrophil count of 1 x 109/L and a platelet count of 100 x 109/L.
* Lansky/Karnofsky score of, at least, 70.
* History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥200 cm/sec by the non-imaging technique measured at a minimum of two separate occasions.
* Progression of CNS vasculopathy on MRA determined to be secondary to SCD.
* History of cerebral infarction on brain MRI (overt stroke, or silent stroke if ≥3 mm in one dimension, visible in two planes on fluid-attenuated inversion recovery T2-weighted images).
* History of two or more episodes of Acute Chest Syndrome (ACS) in lifetime.
* History of three or more SCD pain events requiring treatment with an opiate or IV pain medication in lifetime.
* History of any hospitalization for a complication secondary to SCD (does NOT include empiric hospitalizations for fever only).
* History of two or more episodes of priapism.
* Administration of regular RBC transfusions (≥8 transfusions episodes in the previous 12 months).
* At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.
* Clinically significant neurologic event (overt stroke).
* History of two or more episodes of ACS in the 2-year period preceding enrollment.
* History of three or more SCD pain events requiring treatment with an opiate or IV pain medication (inpatient or outpatient) in the 1-year period preceding enrollment.
* History of any hospitalization for SCD pain or ACS while receiving hydroxyurea treatment.
* History of two or more episodes of priapism (erection lasting ≥4 hours or requiring emergent medical care).
* Administration of regular RBC transfusions (≥8 transfusions in the previous 12 months)
* At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.

* Life expectancy less than 6 month
* Pregnant or breastfeeding patients.
* Infectious Disease: Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning. Patients with confirmed seropositivity for HIV and patients with active or resolved Hepatitis B or C determined by serology and/or NAAT are excluded.
* Liver: Direct (conjugated) bilirubin \> 1.5 mg/dL. Transaminases \>5x upper limit of normal for age.
* Cardiac: Left ventricular shortening fraction \<25% or ejection fraction \<50% by ECHO. Uncontrolled cardiac arrhythmia.
* Kidney: Estimated creatinine clearance less than 60 mL/min/1.73m2.
* Pulmonary function: Diffusion capacity of carbon monoxide (DLCO) \<35% (adjusted for hemoglobin). Baseline oxygen saturation \<94% at rest or PaO2 \<70. Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.
* Heme: Available, medically suitable, and equivalent HLA-matched sibling donor, who does not have major ABO incompatibility or express RBC antigens against which the patient is alloimmunized.

Contacts and Locations

Study Contact

Robert Nickel, MD

CONTACT

202-476-3122

rnickel@childrensnational.org

Maryanne Odinakachukwu

CONTACT

202-476-2957

modinakach@childrensnational.org

Principal Investigator

Robert Nickel, MD

PRINCIPAL_INVESTIGATOR

Children's National Research Institute

Study Locations (Sites)

Children's National Hospital

Washington, District of Columbia, 20010

United States

Collaborators and Investigators

Sponsor: Children's National Research Institute

Robert Nickel, MD, PRINCIPAL_INVESTIGATOR, Children's National Research Institute

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 Date2024-04-03

Study Completion Date2054-09

Study Record Updates

Study Start Date2024-04-03

Study Completion Date2054-09

Terms related to this study

Keywords Provided by Researchers

Sickle Cell Disease
ABO Mismatch
SUN-RAY
Matched Sibling Donor (MSD)

Additional Relevant MeSH Terms

Sickle Cell Disease