MiniClini: Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Completed
• CT.gov ID: NCT02277639
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 52
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with CD3+ /CD19+ depleted peripheral stem cell grafts from mismatched donors. There are two conditioning regimens depending upon patient diagnosis and age.

Condition or Disease	Intervention/Treatment	Phase
Bone Marrow Failure Syndromes; Immunodeficiencies; Immune Dysregulation Syndromes	Device: CliniMACs device	Phase 2

Detailed Description

This study will allow transplantation using a reduced intensity conditioning regimen for children with non-malignant diseases who lack a matched related or unrelated donor. Donors will be unrelated or partially matched related, depending upon urgency and availability. If each parent is haploidentical, the mother will be preferred, as there is evidence of reduced transplant related mortality and superior survival with a maternal donor. The risks of severe graft vs host disease (GVHD) and Epstein-Barr lymphoproliferative disorder will be reduced or eliminated by T and B cell depletion using the Miltenyi Clinimacs device. Patients with bone marrow failure syndromes, who are at high risk for rejection, will undergo pre-conditioning immune suppression with Thymoglobulin. It is recommended that patients with immunedysregulation syndromes receive pre-RIC alemtuzumab as this may reduce the risk on non-engraftment and hyperinflammatory states.

Post-transplant immune suppression will be used to prevent GVHD, as CD3 depletion does not deplete as completely as CD34+ selection. It will be rapidly weaned if no GVHD by day 100 to allow immune reconstitution.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Reduced Intensity Conditioning for Patients With Non-Malignant Diseases Using CD3+/CD19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bone Marrow Failure Syndrome Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion.	Device: CliniMACs device; Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Experimental: Immunodeficiency / Dysregulation Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion.	Device: CliniMACs device; Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Engraftment [One Year]

   The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 22 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Bone marrow failure syndromes for which SCT is indicated, including severe aplastic anemia refractory to non transplant therapies congenital neutropenia, congenital thrombocytopenia, congenital red cell aplasia

• Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is indicated, including severe combined immunodeficiencies, Wiskott-Aldrich syndrome, IPEX syndrome, X-linked lymphoproliferative disease

• Immune dysregulation syndromes, including refractory or recurrent hemophagocytic lymphohistiocytosis, HLH with genetic mutations, refractory multisystemic Langerhans cell histiocytosis, other MAS refractory to standard therapy

• Organ function clearance

Exclusion Criteria:

• Uncontrolled bacterial, viral or fungal infections

• HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.

• Fanconi's syndrome, dyskeratosis congenita or other chromosomal fragility syndromes

• Pregnant Females

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia

Investigators

• Principal Investigator: Nancy Bunin, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nancy Bunin, BMT Medical Director, Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT02277639
• Other Study ID Numbers: 11-008330; CHP 980
• First Posted: Oct 29, 2014
• Last Update Posted: Apr 11, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Nancy Bunin, BMT Medical Director, Children's Hospital of Philadelphia: Transplant related mortality; Graft versus host disease; Bone marrow transplant
• Additional relevant MeSH terms: Bone Marrow Failure Disorders; Pancytopenia; Syndrome

Study Results

Participant Flow

Arm/Group Title	Bone Marrow Failure Syndrome	Immunodeficiency / Dysregulation
Arm/Group Description	Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.	Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Period Title: Overall Study
STARTED	0	2
COMPLETED	0	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Bone Marrow Failure Syndrome	Immunodeficiency / Dysregulation	Total
Arm/Group Description	Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.	Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.	Total of all reporting groups
Overall Participants	0	2	2
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	9.5	9.5
Sex: Female, Male (Count of Participants)
Female	1 Infinity	1 50%
Male	1 Infinity	1 50%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Engraftment
Description	The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.
Time Frame	One Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bone Marrow Failure Syndrome	Immunodeficiency / Dysregulation
Arm/Group Description	Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.	Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Measure Participants	0	2
Count of Participants [Participants]	2 Infinity

Adverse Events

Arm/Group Title	Bone Marrow Failure Syndrome		Immunodeficiency / Dysregulation
Arm/Group Description	Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.		Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
All Cause Mortality
	Bone Marrow Failure Syndrome		Immunodeficiency / Dysregulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/2 (0%)
Serious Adverse Events
	Bone Marrow Failure Syndrome		Immunodeficiency / Dysregulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Bone Marrow Failure Syndrome		Immunodeficiency / Dysregulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.