Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells

Launched by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI) · Jul 31, 2010

Keywords

ClinConnect Summary

This clinical trial is studying a new method of stem cell transplantation aimed at treating severe blood diseases like severe aplastic anemia and myelodysplastic syndrome (MDS). The trial is looking at how using a modified approach to collect stem cells and white blood cells from donors can help reduce complications, such as severe side effects or transplant rejection, in patients receiving the transplant. By carefully selecting and minimizing the number of certain white blood cells, researchers hope to improve the safety and success of the transplant process.

To be eligible, participants must be between 4 and 80 years old and have a diagnosed blood disease that can be treated with a stem cell transplant. They will receive treatment at the National Institutes of Health Clinical Center, where they will undergo a series of preparations before receiving the stem cell transplant, including chemotherapy to prepare their bodies. After the transplant, patients will stay in the hospital for up to a month for monitoring and will continue to have follow-up visits for up to three years to assess the transplant's success and manage any side effects. This trial is currently recruiting participants, so if you or someone you know might be interested, it’s important to discuss it with a healthcare provider.

Gender

ALL

Eligibility criteria

• * INCLUSION CRITERIA:
• * Recipient:
• * Patients diagnosed with one of the following hematologic diseases which are associated with reasonable longevity, shown to be curable by allogeneic BMT but where concern for a high procedural mortality with conventional BMT may delay or prevent such treatment:
• • 1) Paroxysmal nocturnal hemoglobinuria (PNH) associated with life-threatening thrombosis, and/or cytopenia, and/or transfusion dependence and/or recurrent and debilitating hemolytic crisis
• • 2) Severe aplastic anemia (SAA) or pure red cell aplasia (PRCA \[acquired or congenital\]) with bone marrow cellularity \<30% (excluding lymphocytes) associated with RBC or platelet transfusion dependence and/or neutropenia (absolute neutrophil count \<=1000 cells/uL or for patients receiving granulocyte transfusions, absolute neutrophil count \<=1000 cells/ uL before beginning granulocyte transfusions). in newly diagnosed patients and/or in patients who have failed immunosuppressive therapy.
• • 3) Refractory anemia (RA) or RARS MDS patients who have associated transfusion dependence and/or neutropenia.
• • Ages 4 to 80 (both inclusive), and weight \>15 kg
• • Availability of HLA identical or single HLA locus mismatched family donor or 10/10 matched unrelated donor at the allelic level (HLA alleles A, B, C, DR, and DQ).
• • 9/10 donors where all the HLA sequences have the same antigen/peptide binding domains in key exons to the patient. This can result in identical protein sequences between patient and donor. Allele mismatches in p and g groups can be considered acceptable due to the exact matching which exists in the binding domains.
• • Telomere Length Testing
• • Germline/Inherited gene panel in patients where a suspicion for a familial bone marrow failure syndrome (BMFS) exist, hTERC and hTERT, GATA2 mutation testing will be performed on protocol 04-H-0012 or performed elsewhere prior to enrolling on 04-H-0012.
• EXCLUSION CRITERIA:
• • - Recipient: any of the following
• • Major anticipated illness or organ failure incompatible with survival from PBSC transplant
• • Diffusion capacity of carbon monoxide (DLCO) \<40% predicted (patients under the age of 10 may be excluded from this criterion if they have difficulty performing the test correctly and thus are unable to have their DLCO assessed) using DL Adj and DL/VA/Adj.
• • Left ventricular ejection fraction \<40% (evaluated by ECHO)
• • Serum creatinine greater than 2.5mg/dl or creatinine clearance less than 50 ml/min by 24 hr urine collection
• • Serum bilirubin greater than 4 mg/dl, transaminases greater than 5 times the upper limit of normal
• • Pregnant or lactating
• • Fanconi s anemia (test to be performed at a CLIA-certified laboratory)
• • ECOG performance status of 3 or more (See NIH Bone \& Marrow Transplant Consortium Supportive Care Guidelines for HSCT Recipients or Institutional Guidelines for bone and marrow transplants)
• • Other malignant diseases liable to relapse or progress within 5 years, with the exception of a separate hematologic malignancy where allogeneic stem cell transplant has been shown to be potentially curative.
• • Presence of an active infection not adequately responding to appropriate therapy.
• • Inability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects age 8 -17 years with formal consent being obtained from parents or legal guardian.
• INCLUSION CRITERIA:
• -Related Donor:
• • Related donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood samples for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all related donors, but study participation is not required for a donor to make a stem cell donation, so it is possible that not all related donors will enroll onto this study
• • Age greater than or equal to 4 and less than or equal to 80 years old
• EXCLUSION CRITERIA:
• • -Related Donor: None
• • INCLUSION CRITERIA \& EXCLUSION CRITERIA: Unrelated Donor
• • - The NMDP unrelated donor inclusion criteria will be used as outlined in document (http://bethematch.org/WorkArea/DownloadAsset.aspx?id=1960). Donor eligibility will be completed per NMDP standards and in accordance with most recent and stringent FDA guidelines.