NCT05392894

Brief Summary

The purpose of this clinical trial is to evaluate the clinical and cost effectiveness of Haploidentical Stem Cell Transplantation (SCT) for adults with severe sickle cell disease (SCD), who have failed other therapies or are intolerant of existing therapies or require chronic transfusions to prevent on-going complications of SCD.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P25-P50 for phase_3

Timeline
10mo left

Started Feb 2023

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress80%
Feb 2023Mar 2027

First Submitted

Initial submission to the registry

May 23, 2022

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 26, 2022

Completed
9 months until next milestone

Study Start

First participant enrolled

February 23, 2023

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2027

Last Updated

May 10, 2023

Status Verified

May 1, 2023

Enrollment Period

4 years

First QC Date

May 23, 2022

Last Update Submit

May 9, 2023

Conditions

Sickle Cell Disease

Keywords

SickleHaploidenticalStem cellTransplant

Outcome Measures

Primary Outcomes (1)

  • Treatment failure or mortality

    Treatment failure is defined as occurrence of vaso-occlusive crisis, or transfusion from 6 months post-randomisation.

    24 months post-randomisation

Secondary Outcomes (13)

  • Health related quality of life

    At 3, 6, 9, 12, 15, 18, 21 and 24 months post-randomisation

  • All cause mortality

    24 months post-randomisation

  • Sickle Cell Disease-related mortality (excluding transplant related complications)

    24 months post-randomisation

  • Sickle type haemoglobin percentage (HbS%)

    At 6, 12 and 24 months post-randomisation

  • Sickle cell disease related complications

    24 months post-randomisation

  • +8 more secondary outcomes

Study Arms (2)

Standard of care

ACTIVE COMPARATOR

The comparator arm is standard medical care for this patient population. Standard medical care may include all currently available non-trial therapies for SCD.

Other: Standard medical care

Haploidentical stem cell transplantation

EXPERIMENTAL

Participants receiving Haploidentical Stem Cell Transplantation will receive the transplant conditioning regimen as per the standard transplant protocol. Stem cells from a haploidentical donor will be infused on Day 0 according to standard institutional practices. Bone marrow is the preferred stem cell source however peripheral blood may be used as an alternative where required due to donor reasons.

Procedure: Haploidentical stem cell transplantation

Interventions

Haploidentical stem cell transplantationPROCEDURE

Stem cell transplant from bone marrow or peripheral blood from haploidentical donor using standard nationally approved transplant procedure.

Haploidentical stem cell transplantation
Standard medical careOTHER

Standard medical care may include any currently available therapies for SCD patients. These may or may not include regular elective transfusion therapy or medications such as hydroxycarbamide.

Standard of care

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult patients age ≥ 18 years
  • Confirmed haploidentical donor
  • Severe SCD phenotype who are at high risk for morbidity and mortality. Severe SCD is defined by at least one of the following:
  • i. Clinically significant neurologic event (stroke) or deficit lasting \> 24 hours.
  • ii. History of ≥2 acute chest syndromes in a 2-year period preceding enrolment despite optimum treatment, e.g. with hydroxycarbamide (HC).
  • iii. History of ≥3 severe pain crises per year in a 2-year period preceding enrolment despite the institution of supportive care measures (e.g. optimum treatment with HC).
  • iv. Administration of regular transfusion therapy (=8 packed red blood transfusions per year for 1 year to prevent vaso-occlusive complications).
  • v. Patients assessed as requiring transfusion but with red cell allo-antibodies/very rare blood type, rendering it difficult to continue/commence chronic transfusion.
  • vi. Patients requiring HC/transfusion for treatment of SCD complications who cannot tolerate either therapy due to significant adverse reactions.
  • vii. Established end organ damage relating to SCD, including but not limited to progressive sickle vasculopathy and hepatopathy. End-organ sufficient for entry to this trial shall be ratified at the UK NHP.
  • d) Patients must be fit to proceed to Haploidentical SCT as defined below: i. Karnofsky score ≥60 ii. Cardiac function: LVEF ≥45% or shortening fraction ≥25% iii. Lung Function: FEV1, FVC and TLCO ≥50% iv. Renal function: EDTA GFR ≥40 ml/min/1.73m2 v. Hepatic function: ALT \<x3 ULN and bilirubin \<x2 the upper limit of normal, those with hyperbilirubinemia due to sickle related haemolysis will not be excluded. No radiological evidence of cirrhosis.
  • e) Written informed consent.

You may not qualify if:

  • Fully matched sibling donor.
  • Previous bone marrow transplant.
  • Pregnancy or breast feeding.
  • Participants able to conceive a child that are unprepared to use effective contraception.
  • Clinically significant donor specific HLA antibodies.
  • HIV infection or active Hepatitis B or C.
  • Uncontrolled infection including bacterial, fungal and viral.
  • Participation in another interventional trial in the last three months.
  • Pre-existing condition deemed to significantly increase the risk of Haploidentical SCT by the local Principal Investigator.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

King's College Hospital

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

  • Ann-Marie Murtagh

    King's College Hospitals NHS Foundation Trust

    STUDY DIRECTOR

Central Study Contacts

Victoria Potter, BSc, MBBS, FRACP, FRCPA

CONTACT

+44 20 3299 3730victoriapotter@nhs.net

Daryl Hagan, BSc, MSc

CONTACT

+44 20 7848 0532redress@kcl.ac.uk

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 23, 2022

First Posted

May 26, 2022

Study Start

February 23, 2023

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Last Updated

May 10, 2023

Record last verified: 2023-05

Locations

GB(1)