Stem Cell Transplant in Patients With Severe Sickle Cell Disease

NCT03421756 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: HCC 17-097
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective pilot study of matched-related donor allogeneic stem cell transplantation in adults with severe sickle cell disease using a matched-sibling PBSC graft with a non-myeloablative conditioning regimen (Alemtuzumab).

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Treatment Success

  Evaluating reversal of Hb S % to that of the donor's phenotype, in recipients of HLA matched-sibling peripheral blood - hematopoietic stem cell transplantation (HSCT) with NMA conditioning regimen. Testing for treatment success will include Hb Electrophoresis. Recipients with donors AA should have nearly 0% Hb S. Recipients with donors AS should have similar Hb S % (approximately \< 60%) as the donor. The proportion of patients experiencing treatment success, will be calculated with a 90% exact confidence interval.

  up to 1 year after HSCT

Secondary Outcomes (13)

• Engraftment

  up to 1 year after HSCT

• Probability of developing acute GVHD after HSCT.

  up to 100 days after HSCT

• Probability of developing chronic GVHD after HSCT.

  up to 2 years after HSCT

• Graft failure or Relapse

  up to 2 years after HSCT

• Discontinuation of Immunosuppressive therapy

  up to 2 years after HSCT

Study Arms (1)

Non Myeloablative regimen (Alemtuzumab)

EXPERIMENTAL

Sickle cell patient receives sibling donor peripheral blood stem cell transplant with non-myeloablative pre-transplant conditioning.

Drug: Alemtuzumab; Radiation: Total Body Irradiation; Drug: Sirolimus

Interventions

Alemtuzumab DRUG

Alemtuzumab is a non-myeloablative pre-transplant conditioning regimen. Non-myeloablative therapy uses doses of chemotherapy and radiation to weaken (but not destroy) the patients bone marrow and immune system, while still allowing their body will accept the donor's stem cells. Alemtuzumab will be given 7 days prior to stem cell infusion at 0.03 mg/kg IV, 6 days prior to stem cell infusion at 0.1 mg/kg IV, and 5 thru 3 days prior to stem cell infusion at 0.3 mg/kg IV.

Non Myeloablative regimen (Alemtuzumab)

Total Body Irradiation RADIATION

300 cGy will be administered in a single fraction on Day - 2. TBI is used commonly as part of pre-transplant conditioning in a variety of settings.

Also known as: TBI

Non Myeloablative regimen (Alemtuzumab)

Sirolimus DRUG

Sirolimus will be used for the prevention of graft-verus-host disease and will begin on Day - 1.

Also known as: Rapammune

Non Myeloablative regimen (Alemtuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient selection
• Age \> 18 years
• Patients with Hb SS, Hb SC, Hb Sβ0 genotype
• Presence of at least 1 of the following manifestations:
• History of clinically significant neurologic event defined as stroke or any neurological deficit lasting \> 24 hours.
• History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures
• Three or more pain crises per year in the 2-year period preceding referral (required intravenous pain management in the outpatient or inpatient hospital setting).
• This may include painful episodes related to priapism, osteonecrosis or any sickle-related complication.
• An echocardiographic finding of the tricuspid valve regurgitant jet (TRJ) velocity ≥ 2.7 m/sec.
• History of osteonecrosis or avascular necrosis of ≥ 2 joints
• Administration of regular 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)
• History of RBC allo-immunization but without detectable allo-antibodies.
• Evidence of sickle hepatopathy or iron overload in patients who received ≥ 8 packed RBC transfusions for ≥ 1 year or have received ≥ 20 cumulative packed RBC transfusions. These patients will undergo MRI of the liver to estimate liver iron content.
• Patients with hepatic iron content of ≤ 7 mg Fe/ gm of liver will be included ii. Patients with hepatic iron content of ≥ 7 mg Fe/ gm of liver will undergo biopsy to look for absence of histological findings suggestive of cirrhosis, fibrosis and active hepatitis
• h. Sickle nephropathy defined as Cr ≥ 1.5 times the ULN or biopsy proven i.Reversible SCD complication not ameliorated by hydroxyurea: i.Two or more vaso-occlusive crises requiring hospitalizations ii. Any episode of ACS while on hydroxyurea

You may not qualify if:

• Patient selection
• Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
• Seropositivity for HIV.
• Previous stem cell transplantation.
• Participation in a clinical trial in which the patient received an investigational drug or device
• A history of substance abuse as defined by version IV of the Diagnostic \& Statistical Manual of Mental Disorders (DSM IV).
• Demonstrated lack of compliance with prior medical care as determined by referring physician.
• Pregnant or breast-feeding females.
• Unwillingness to use approved contraception method from time of conditioning regimen and 4 months after discontinuation of all immunosuppressive medications.
• Siblings who are ≥18 years and capable and willing to donate PBSC
• Sibling donors are HLA-matched. HLA-A, B, C, and DRB1 match based on high-resolution typing
• All sibling donors MUST meet institutional criteria for donation.
• Donors with sickle cell trait (Hb AS) are permitted.
• Donors with ABO minor incompatibility are permitted
• Donors with hemoglobinopathies: Hb SS, Hb SC, Hb Sβ0 and all other unstable hemoglobins

Sponsors & Collaborators

• Kathleen Dorritie: lead

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Alemtuzumab; Whole-Body Irradiation; 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; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Organic Chemicals

Study Officials

• Kathleen Dorritie, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: February 5, 2018
• Study Start: March 29, 2018
• Primary Completion: September 15, 2018
• Study Completion: May 15, 2022
• Last Updated: June 28, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)