Haploidentical Hematopoietic Stem Cell Transplantation

NCT02165007 | Completed Phase 1 DMC

• 1 other identifier: HAPSICKLE
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed as a Pilot/Phase 1 trial of reduced intensity Haploidentical HSCT in patients with sickle cell disease and thalassemia. The purpose of the study is to assess the safety and toxicity of reduced intensity conditioning haploidentical hematopoietic stem cell transplantation.

Conditions

Sickle Cell-thalassemia Disease; Thalassemia

Outcome Measures

Primary Outcomes (1)

• Incidence of transplant related adverse outcomes

  The primary endpoint of this trial is safety. Transplant related adverse outcomes and non-hematological toxicity will be measured through Day +60 on this objective to include: * Non-hematological severe (Grade IV and V) organ specific toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0) * Rates of non-engraftment * Severe acute (Grade III-IV) * Veno-occlusive disease of the liver * Idiopathic pneumonia syndrome * Seizures/Posterior reversible encephalopathy syndrome (PRES)

  60 days

Secondary Outcomes (1)

• Overall survival

  2 years

Other Outcomes (6)

• Graft failure

  2 years

• Grades II-IV and III-IV acute GVHD

  180 days

• Chronic GVHD

  1 year

Study Arms (1)

peripheral blood stem cell graft that are CD34+ selected

EXPERIMENTAL

peripheral blood stem cell graft that are CD34+ selected. All patients will undergo reduced intensity conditioning regimen which followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device and Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year (see intervention).

Drug: peripheral blood stem cell graft that are CD34+ selected

Interventions

peripheral blood stem cell graft that are CD34+ selected DRUG

The preparatory regimen will consist of Hydroxyurea from Days -50 to -22, Alemtuzumab from days -21 to -19 (test dose Alemtuzumab on day -22), Fludarabine days -8 to -4, Thiotepa Day -4, Melphalan day -3 to -2 (Table 4a). In patients with intolerance to or have received alemtuzumab in the prior 6 months, alemtuzumab will be replaced with rabbit ATG on days -10 through -7, followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device. Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year.

Also known as: Reduced intensity conditioning, Sirolimus

peripheral blood stem cell graft that are CD34+ selected

Eligibility Criteria

• Age: Up to 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• First allogeneic transplant
• Age up to 22 years
• Patients with severe sickle cell disease (stroke, elevated TCD velocities, \>2 acute chest syndrome, ongoing chronic red cell transfusion \> 6 months)
• Patients with transfusion dependent thalassemia and evidence of iron overload
• Patients must have a related donor that is HLA-matched at \>/=4 of 8 but \<8/8 HLA-A, -B, -C and -DRB1
• Cardiac function: Shortening fraction \>25%; ejection fraction \>40%
• Estimated creatinine clearance greater than 50 mL/minute
• Pulmonary function: DLCO ≥40% (adjusted for hemoglobin) and FEV1≥50% in patients 7 years and older with normal cognitive function and able to perform the test adequately. If not able to complete the testing a CT chest will be required., oxygen saturation\>91%
• Liver function: direct (conjugated) bilirubin \< 2x the upper limit of normal and ALT/AST \< 2.5x the upper normal limit.
• Signed informed consent.

You may not qualify if:

• Life expectancy less than 6 months
• Patients with 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.
• Pregnant or breastfeeding patients
• Patients seropositive for the human immunodeficiency virus (HIV)
• Patient with active Hepatitis B or C determined by serology and/or NAAT
• Active hepatitis, bridging fibrosis or cirrhosis on liver biopsy (biopsy required for patients on chronic transfusion therapy for \> 1 year and evidence of iron overload with ferritin \>1000 ng/mL)
• Patients with suitable 8/8 HLA matched related and unrelated donors
• Patients who have an intolerance to or have received alemtuzumab in the prior 6 months will be excluded from enrollment unless alemtuzumab is replaced with rabbit ATG in the conditioning regimen

Sponsors & Collaborators

• Catherine Bollard: lead
• Children's National Research Institute: collaborator

Study Sites (1)

Childrens National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (1)

• Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.

  PMID: 36240296 DERIVED

MeSH Terms

Conditions

Thalassemia

Interventions

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)

Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director- Center for Cancer and Immunology Research

Study Record Dates

• First Submitted: June 13, 2014
• First Posted: June 17, 2014
• Study Start: January 1, 2015
• Primary Completion: January 1, 2024
• Study Completion: October 1, 2024
• Last Updated: December 19, 2024

Record last verified: 2024-12

Locations

US (1)