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SCD-Haplo: Phase II Study of HLA-Haploidentical SCT for Aggressive SCD (SCD-Haplo)

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ClinicalTrials.gov Identifier: NCT02013375
Recruitment Status : Active, not recruiting
First Posted : December 17, 2013
Last Update Posted : April 20, 2017
Sponsor:
Information provided by (Responsible Party):
Damiano Rondelli, MD, University of Illinois at Chicago

Brief Summary:
Related donor stem cell transplantation using the alemtuzumab/ TBI platform has been shown to be a safe strategy to cure severe sickle cell disease. However, due to a lack of suitable donors, many patients cannot benefit from this strategy. Alternative donor sources are desperately needed to fill this gap. Nearly all patients will have a haploidentical family member who would be able to donate. The use of post transplantation cyclophosphamide has greatly improved the outcome of haploidentical stem cell transplantation. The investigators propose to combine this with alemtuzumab/TBI conditioning.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Procedure: Haploidentical Transplant Drug: Alemtuzumab Radiation: Total Body Irradiation Drug: Cyclophosphamide Drug: Sirolimus Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: SCD-Haplo: A Phase II Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
Actual Study Start Date : February 5, 2014
Estimated Primary Completion Date : October 1, 2018
Estimated Study Completion Date : October 1, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Haploidentical Transplant
All subjects will undergo pre-conditioning treatment with alemtuzumab (0.3 mg/kg Day -5, Day -4, Day -3) and total body irradiation (300cGy), followed by stem cell transplant, and post-transplant treatment with cyclophosphamide (50mg/kg/day) and sirolimus (target trough level of 10-15ng/mL).
Procedure: Haploidentical Transplant
All subjects will undergo pre-conditioning treatment with alemtuzumab (0.3 mg/kg Day -5, Day -4, Day -3) and total body irradiation (300cGy), followed by stem cell transplant, and post-transplant treatment with cyclophosphamide (50mg/kg/day) and sirolimus (target trough level of 10-15ng/mL).
Other Name: Mismatched allogeneic bone marrow transplant

Drug: Alemtuzumab
On Day -7, the first test dose of alemtuzumab (0.03 mg/kg) will be administered and on Day -6, the second test dose of alemtuzumab (0.1 mg/kg) will be administered. Alemtuzumab (0.3 mg/kg) will be infused daily on Day -5, -4, and -3.
Other Name: Campath®

Radiation: Total Body Irradiation
A 300cGy dose of TBI will be administered in a single fraction on Day -2.

Drug: Cyclophosphamide
Cyclophosphamide (50 mg/kg IBW) IV, over approximately 1-2 hours, is given on Day 3 post-transplantation (ideally between 60 and 72 hours after marrow infusion) and on Day 4 (approximately 24 hours after Day 3 cyclophosphamide).
Other Name: Cytoxan®

Drug: Sirolimus
Sirolimus will be started on Day +5 (at least 24 hours after the completion of the cyclophosphamide infusion). The starting dose will be 12mg followed by 4mg PO daily. Doses will be adjusted to achieve a whole blood trough level of 4 - 12ng/mL.
Other Name: Rapamune®




Primary Outcome Measures :
  1. Engraftment Rate [ Time Frame: Up to Day 60 post-transplant. ]
    To determine the engraftment at Day +60 following HLA-haploidentical hematopoietic stem cell transplant protocol using immunosuppressive agents and low-dose total body irradiation (TBI) for conditioning and post-transplant cyclophosphamide in patients with sickle cell disease.


Secondary Outcome Measures :
  1. Acute & Chronic Complications [ Time Frame: Up to one year post-transplant ]
    To assess the frequency of acute and chronic complications of sickle cell disease during and after HLA-haploidentical hematopoietic stem cell transplantation with this protocol. The acute complications include vaso-occlusive pain episodes, acute chest syndrome, stroke, and priapism. The chronic complications include nephropathy, retinopathy, osteonecrosis, pulmonary artery pressures, cardiomyopathy, and chronic lung disease.

  2. Overall & Disease-Free Survival [ Time Frame: Up to one year post-transplant. ]
    To determine the overall and disease-free survival of patients with sickle cell disease receiving HLA-haploidentical hematopoietic stem cell transplantation with this protocol.

  3. Morbidity & Mortality [ Time Frame: Up to one year post-transplant. ]
    To determine the incidence of acute and chronic graft-versus-host disease, the incidence of infectious complications, and the transplant related mortality in sickle cell disease patients after HLA-haploidentical hematopoietic stem cell transplantation with this protocol.



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Ages Eligible for Study:   16 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Patient Eligibility:

  • Patients with sickle cell disease are eligible if they have any of the following complications:

    • Stroke or central nervous system event lasting longer than 24 hours
    • Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year requiring emergency room, acute care center, or hospital admissions.
    • Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits
    • Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events
    • Red-cell alloimmunization (≥ 2 antibodies) during long-term transfusion therapy
    • Bilateral proliferative retinopathy with major visual impairment in at least one eye
    • Osteonecrosis of 2 or more joints
    • Sickle cell nephropathy, defined by a GFR < 90mL/min/1.73m2 or the presence of macroalbuminuria (urine albumin > 300 mg/g creatinine)
    • Pulmonary hypertension, defined by a mean pulmonary artery pressure > 25mmHg
  • Age 16-60 years
  • Karnofsky performance status of 60 or higher
  • Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40%
  • Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50% predicted (after adjustment for hemoglobin concentration)
  • Estimated GFR ≥ 50mL/min as calculated by the modified MDRD equation
  • ALT ≤ 3x upper limit of normal
  • HIV-negative
  • Patient is pregnant
  • Patient is able and willing to sign informed consent
  • Patient has an HLA-haploidentical relative

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02013375


Locations
United States, Illinois
University of Illinois Cancer Center
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
Damiano Rondelli, MD
Investigators
Principal Investigator: Damiano Rondelli, MD University of Illinois at Chicago

Responsible Party: Damiano Rondelli, MD, Chief, Division of Hematology & Oncology, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT02013375     History of Changes
Other Study ID Numbers: 2013-0849
First Posted: December 17, 2013    Key Record Dates
Last Update Posted: April 20, 2017
Last Verified: April 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Cyclophosphamide
Sirolimus
Everolimus
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents