Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00244010
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 40
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Due to an overall and disease free survival of 85% to 100%, allogeneic blood or bone marrow stem cell transplantation using an HLA matched sibling donor is the therapy of choice for patients with severe aplastic anemia (SAA). Unfortunately, only about 25% of patients have such a donor. For patients with SAA lacking a matched sibling donor, immunosuppressive therapy is the current treatment of choice. Approximately 70% of these patients have a complete or partial response to immunosuppressive therapy, achieving transfusion independence and/or growth factor independence.

For the approximately 30% of patients who do not respond to immunosuppressive therapy or experience recurrence, alternative donor (matched unrelated, partially matched family member) transplantation is a treatment option. However, graft rejection and graft-versus-host-disease (GVHD) are significant barriers to success, decreasing event-free survival to 30% to 50%.

This study offers stem cell transplantation using a partially matched family member (haploidentical) donor to those patients with no available HLA-matched sibling or matched unrelated donor. In an attempt to reduce GVHD and regimen-related toxicity while maintaining adequate engraftment, we plan to infuse a highly purified stem cell graft. The Miltenyi Biotec CliniMACS CD3 depletion system will be used to derive a defined allogeneic graft highly enriched for CD34+ hematopoietic cells and depleted of CD3+ T-lymphocytes from G-CSF mobilized, donor-derived peripheral blood stem cells.

Patients 21 years of age and younger with refractory cytopenias are also eligible for this protocol as there are no other potentially curative therapies currently available for these conditions.

The primary objective of this study is to evaluate the safety of transplantation using a haploidentical donor product engineered to targeted cell counts using the investigational CliniMACS device for patients with refractory severe aplastic anemia (SAA) or refractory cytopenias. The treatment plan would be considered unsafe if we can find this type of procedure is associated with a significantly higher treatment failure rate. Treatment failure is defined as any occurrence of the following events, overall grade III-IV acute GVHD, graft failure or death due to any cause within 100 days after transplant.

Condition or Disease	Intervention/Treatment	Phase
Anemia, Aplastic; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Kostmann Syndrome	Device: Allogeneic stem cell transplant	N/A

Detailed Description

Secondary objectives for this protocol include the following:

• To observe the degree of hematopoietic chimerism in T-cells during the first year posttransplant.

• To observe the relative proportions of donor/host T-regulatory cells during the first year posttransplant.

• To monitor rates of acute and chronic GVHD during the first year posttransplant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hematopoietic Stem Cell Transplantation (HSCT) From Partially Matched Family Donors for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias: A Pilot Study
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Other: 1

Device: Allogeneic stem cell transplant; Participants will receive a reduced intensity conditioning regimen consisting of fludarabine, thiotepa, melphalan, and OKT3 followed by an infusion of haploidentical stem cells. Rituximab will be administered within 24 hours of the infusion in an effort to prevent posttransplant lymphoproliferative disorder LPD. In addition to T-cell depletion of the donor product, participant will receive mycophenolate mofetil for prophylaxis of GVHD.; Other Names: Allogeneic stem cell transplantation Haploidentical stem cell transplant T-cell depletion Partially matched family member donor transplant Hematopoietic stem cell transplant

Outcome Measures

Primary Outcome Measures

1. Treatment Failures [100 days post transplant]

   The primary objective of this study is to evaluate the safety of HAPLO HSCT for patients with refractory severe aplastic anemia (SAA) or refractory cytopenias. The treatment plan would be considered unsafe if we can demonstrate that it is associated with a significantly higher treatment failure rate. The treatment failure is defined as any occurrence of the following events, overall grade III-IV acute GVHD, graft failure or death due to any cause within 100 days post HSCT or after the last cellular product infusion, if required.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• One of the following diagnoses:

• Refractory severe aplastic anemia

• Refractory Kostmann syndrome

• Refractory Diamond-Blackfan anemia

• Refractory amegakaryocytic thrombocytopenia

• Absence of a suitable HLA-matched sibling donor and absence of a 10/10 allele matched unrelated donor.

• Life expectancy of greater than six weeks as per the judgment of the principal investigator.

• Karnofsky or Lansky Performance Status score of greater than or equal to 70%.

• Creatinine clearance is greater than or equal to 40 cc/min/1.73 m2.

• FVC greater than or equal to 40% of predicted or pulse oximetry greater than or equal to 92% on room air.

• Does not have a known allergy to murine products.

Exclusion criteria:

• Ejection fraction or shortening fraction below the lower limit of normal for age.

• Lactating (female patient).

• Pregnant or lactating

• Diagnosis of Fanconi Anemia.

• Positive HLA crossmatch with donor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital

Investigators

• Principal Investigator: Kimberly Kasow, DO, St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• St. Jude Children's Research Hospital

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT00244010
• Other Study ID Numbers: SAAHAP; Severe Aplastic Anemia; Cytopenias
• First Posted: Oct 25, 2005
• Last Update Posted: May 30, 2017
• Last Verified: Feb 1, 2009

• Keywords provided by St. Jude Children's Research Hospital: Aplastic anemia; Amegakaryocytic thrombocytopenia; Diamond-Blackfan Anemia; Kostmann syndrome; Allogeneic stem cell transplantation; Haploidentical stem cell transplant; T-cell depletion; Partially matched family member donor transplant; Refractory cytopenia
• Additional relevant MeSH terms: Anemia; Thrombocytopenia; Anemia, Aplastic; Anemia, Diamond-Blackfan

Study Results

Participant Flow

Recruitment Details	Two patients and two donors were enrolled between 10/24/2005 and 2/24/2009 when the study was closed. The study was terminated due to the PI leaving St. Jude.

Arm/Group Title	Patients	Donors
Arm/Group Description	Patients were enrolled to treat refractory severe aplastic anemia.	Parents of patients were enrolled onto the SAAHAP study to provide hematopoietic stem cells.
Period Title: Overall Study
STARTED	2	2
COMPLETED	2	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Patients	Donors	Total
Arm/Group Description	Patients were enrolled to treat refractory severe aplastic anemia.	Parents of patients were enrolled onto the SAAHAP study to provide hematopoietic stem cells.	Total of all reporting groups
Overall Participants	2	2	4
Age (Count of Participants)
<=18 years	2 100%	0 0%	2 50%
Between 18 and 65 years	0 0%	2 100%	2 50%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 100%	1 50%	3 75%
Male	0 0%	1 50%	1 25%

Outcome Measures

1. Primary Outcome

Title	Treatment Failures
Description	The primary objective of this study is to evaluate the safety of HAPLO HSCT for patients with refractory severe aplastic anemia (SAA) or refractory cytopenias. The treatment plan would be considered unsafe if we can demonstrate that it is associated with a significantly higher treatment failure rate. The treatment failure is defined as any occurrence of the following events, overall grade III-IV acute GVHD, graft failure or death due to any cause within 100 days post HSCT or after the last cellular product infusion, if required.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

Enrollment was terminated due to the PI leaving the institution. Insufficient data was generated to answer the objective.

Arm/Group Title	Patients	Donors
Arm/Group Description	Patients were enrolled to treat refractory severe aplastic anemia.	Parents of patients were enrolled onto the SAAHAP study to provide hematopoietic stem cells.
Measure Participants	0	0

Adverse Events

Time Frame	Two patients and two donors were enrolled between 10/24/2005 and 2/24/2009 when the study was closed.
Arm/Group Title	Patients		Donor
Arm/Group Description	Patients were enrolled to treat refractory severe aplastic anemia.		Donors were not assessed for adverse events.
All Cause Mortality
	Patients		Donor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Patients		Donor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		0/0 (NaN)
Gastrointestinal disorders
Pancreatitis	1/2 (50%)	1	0/0 (NaN)	0
Abdominal Pain (intermittent)	1/2 (50%)	1	0/0 (NaN)	0
Infections and infestations
Cellulitis of skin	1/2 (50%)	1	0/0 (NaN)	0
Infection, Staphylococcus Aureus, Blood	1/2 (50%)	1	0/0 (NaN)	0
Investigations
Methemoglobinemia	1/2 (50%)	1	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Patients		Donor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		0/0 (NaN)
Blood and lymphatic system disorders
Febrile Neutropenia	1/2 (50%)	2	0/0 (NaN)	2
Gastrointestinal disorders
Nausea and Vomiting (intermittent)	1/2 (50%)	1	0/0 (NaN)	1
General disorders
Fever without Neutropenia	1/2 (50%)	1	0/0 (NaN)	1
Hepatobiliary disorders
Hepatomegaly (intermittent)	1/2 (50%)	1	0/0 (NaN)	1
Metabolism and nutrition disorders
Elevated Ferritin Level	1/2 (50%)	1	0/0 (NaN)	1
Hemosiderosis	1/2 (50%)	1	0/0 (NaN)	1
Iron overload (intermittent)	1/2 (50%)	1	0/0 (NaN)	1
Musculoskeletal and connective tissue disorders
Pain-Back	1/2 (50%)	1	0/0 (NaN)	1
Nervous system disorders
Headache	1/2 (50%)	1	0/0 (NaN)	1

Limitations/Caveats

This study has terminated due to the PI leaving the institution. An insufficient number of subjects were enrolled to answer the primary objective.

More Information

Certain Agreements

All Principal Investigators ARE 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.