Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim

NCT01182675 | Terminated Phase 2 Results

• 1 other identifier: UCSF10-00701
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to develop a novel approach to hematopoietic stem cell transplantation for children with Severe Combined Immunodeficiency Disease (SCID) that eliminates the use of toxic chemotherapy conditioning and maximizes the likelihood of T and B cell immune reconstitution. Rather than classic chemotherapeutic agents, the investigators will utilize a targeted stem cell mobilizer, plerixafor, in combination with alemtuzumab, a monoclonal antibody. Correlative scientific questions will include: 1) efficacy and characteristics of host stem cell mobilization; and 2) alemtuzumab pharmacokinetics in very young children.

Conditions

Severe Combined Immunodeficiency

Keywords

SCID; Transplant; Alemtuzumab; Plerixafor

Outcome Measures

Primary Outcomes (1)

• Engraftment of Donor B-cells in Blood by STR Testing

  Number of participants in whom donor B cells were detected in the patient's blood after HSCT.

  1 Year

Secondary Outcomes (5)

• Incidence of Acute GVHD

  100 Days

• Incidence of Chronic GVHD

  2 Years

• Percentage of Patients Who Become Independent From Regular IVIG Infusion

  2 Years

• Number of Patients With Engraftment of Donor Stem Cells in Bone Marrow by STR Testing

  1 Year

• Number of Patients Who Achieve Engraftment of Donor T-cells in Blood by STR Testing

  1 Year

Study Arms (2)

T-cell Graft Permissive SCID

EXPERIMENTAL

Patients with SCID with: i. NK- phenotype; ii. NK+ phenotype with 10/10 HLA-matched relative or unrelated donor; or iii. NK+ phenotype with maternal engraftment by STR analysis and undergoing haplocompatible HSCT from maternal donor Intervention: Transplant Conditioning with Mobilization Only

Drug: Transplant Conditioning with Mobilization Only

T-cell Graft Resistant SCID

EXPERIMENTAL

Patients with SCID with NK+ phenotype with HLA-mismatched donor Intervention: Transplant Conditioning with Mobilization and Alemtuzumab

Drug: Transplant Conditioning with Mobilization and Alemtuzumab

Interventions

Transplant Conditioning with Mobilization Only DRUG

Day -4: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -3: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -2: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -1: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day 0: Plerixafor 240 mcg/kg subcutaneous 9-12 hours prior to transplant; Day 0 Transplant

Also known as: Conditioning with Filgrastim and Plerixafor

T-cell Graft Permissive SCID

Transplant Conditioning with Mobilization and Alemtuzumab DRUG

Day -7: Alemtuzumab 0.3 mg test dose then 0.3 mg/kg IV; Day -6: Alemtuzumab 0.3 mg/kg IV; Day -5: Alemtuzumab 0.3 mg/kg IV; Day -4: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -3: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -2: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -1: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day 0: Plerixafor 240 mcg/kg subcutaneous 9-12 hours prior to transplant; Day 0: Transplant

Also known as: Conditioning with Filgrastim, Plerixafor, and Alemtuzumab

T-cell Graft Resistant SCID

Eligibility Criteria

• Age: Up to 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients with classic SCID phenotype (\<400 CD3/ul or maternally engrafted and \<10% of normal PHA lymphoproliferative response). Genotypic identification is preferable, but not required.
• Patients must have an acceptable stem cell donor (HLA matched relative, 9 or 10/10 HLA-matched unrelated, or haplocompatible relative).

You may not qualify if:

• Patients with "leaky" SCID syndromes, Omenn's Syndrome, reticular dysgenesis, ADA deficiency
• Lansky score \<60%
• Patient with expected survival \<4 weeks (including disseminated CMV infection involving lungs and/or CNS)

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF Benioff Children's Hospital

San Francisco, California, 94143, United States

Location

Related Publications (3)

• Dvorak CC, Hung GY, Horn B, Dunn E, Oon CY, Cowan MJ. Megadose CD34(+) cell grafts improve recovery of T cell engraftment but not B cell immunity in patients with severe combined immunodeficiency disease undergoing haplocompatible nonmyeloablative transplantation. Biol Blood Marrow Transplant. 2008 Oct;14(10):1125-1133. doi: 10.1016/j.bbmt.2008.07.008.

  PMID: 18804042 BACKGROUND

• Dvorak CC, Cowan MJ. Radiosensitive severe combined immunodeficiency disease. Immunol Allergy Clin North Am. 2010 Feb;30(1):125-42. doi: 10.1016/j.iac.2009.10.004.

  PMID: 20113890 BACKGROUND

• Dvorak CC, Cowan MJ. Hematopoietic stem cell transplantation for primary immunodeficiency disease. Bone Marrow Transplant. 2008 Jan;41(2):119-26. doi: 10.1038/sj.bmt.1705890. Epub 2007 Oct 29.

  PMID: 17968328 BACKGROUND

MeSH Terms

Conditions

Severe Combined Immunodeficiency

Interventions

Transplantation Conditioning; Filgrastim; plerixafor; Alemtuzumab

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Christopher C. Dvorak, MD
• Organization: UCSF

dvorakc@peds.ucsf.edu

415-476-2188

Study Officials

• Christopher C Dvorak, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 9, 2010
• First Posted: August 17, 2010
• Study Start: August 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: July 31, 2018
• Results First Posted: November 10, 2014

Record last verified: 2018-07

Locations

US (1)