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

NCT02013375 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2013-0849
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Engraftment Rate

  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.

  Up to Day 60 post-transplant.

Secondary Outcomes (3)

• Acute & Chronic Complications

  Up to one year post-transplant

• Overall & Disease-Free Survival

  Up to one year post-transplant.

• Morbidity & Mortality

  Up to one year post-transplant.

Study Arms (1)

Haploidentical Transplant

EXPERIMENTAL

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

Interventions

Haploidentical Transplant PROCEDURE

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).

Also known as: Mismatched allogeneic bone marrow transplant

Haploidentical Transplant

Alemtuzumab DRUG

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.

Also known as: Campath®

Haploidentical Transplant

Total Body Irradiation RADIATION

A 300cGy dose of TBI will be administered in a single fraction on Day -2.

Haploidentical Transplant

Cyclophosphamide DRUG

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).

Also known as: Cytoxan®

Haploidentical Transplant

Sirolimus DRUG

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.

Also known as: Rapamune®

Haploidentical Transplant

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Damiano Rondelli, MD: lead

Study Sites (1)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Alemtuzumab; Whole-Body Irradiation; Cyclophosphamide; 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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones

Results Point of Contact

• Title: Dr Damiano Rondelli
• Organization: University of Illinois at Chicago

drond@uic.edu

312-996-6179

Study Officials

• Damiano Rondelli, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Hematology & Oncology

Study Record Dates

• First Submitted: December 11, 2013
• First Posted: December 17, 2013
• Study Start: April 10, 2014
• Primary Completion: May 31, 2014
• Study Completion: September 7, 2018
• Last Updated: August 28, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-08

Locations

US (1)