Phase 2
N=31
Stem Cell Transplant Using Peripheral and Cord Blood Stem Cells to Treat Severe Aplastic Anemia and Myelodysplastic Syndrome
Myelodysplastic Syndrome (MDS) With Refractory Anemia (RA) · Severe Aplastic Anemia (SAA)
Bottom Line
View on ClinicalTrials.gov: NCT00604201 ↗Enrolled (actual)
31
Serious AEs
90.3%
Results posted
Jul 2020
Primary outcome: Primary: Number of Participants Who Engrafted by Day 42 — 30 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Umbilical Cord Blood (Biological)
- Age
- Pediatric, Adult, Older Adult · 4+ yrs
- Sex
- All
- Sponsor
- National Heart, Lung, and Blood Institute (NHLBI)
- Primary completion
- Oct 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Engrafted by Day 42 |
30 | — |
| SECONDARY Number of Participants Who Developed Chronic GVHD |
12 | — |
| SECONDARY Number of Participants Who Developed Acute GVHD |
5 | — |
| SECONDARY Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 100 |
1 | — |
| SECONDARY Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 200 |
1 | — |
| SECONDARY Number of Participants Who Had ANC Recovery at Day 22 |
30 | — |
| SECONDARY Number of Participants Who Had Relapse of Disease |
1 | — |
| SECONDARY Number of Participants Who Developed Grade II Acute GVHD |
3 | — |
| SECONDARY Number of Participants Who Developed Grade III Acute GVHD |
2 | — |
| SECONDARY Number of Participants Who Developed Mild Chronic GVHD |
10 | — |
| SECONDARY Number of Participants Who Developed Moderate Chronic GVHD |
2 | — |
| SECONDARY Number of Participants Who Developed Severe Chronic GVHD |
— | — |
| SECONDARY Number of Participants Who Developed Steroid Refractory Acute GVHD |
— | — |
Summary
This study will evaluate the safety and effectiveness of treating patients with severe aplastic anemia (SAA) or myelodysplastic syndrome (MDS) with both peripheral blood stem cells from a family member and umbilical cord blood stem cells from an unrelated donor.
Patients with SAA or MDS for whom other treatments have failed or are not available may be eligible for this study. Candidates may not have a tissue-matched sibling or matched unrelated donor and must have a family member who is a partial tissue type match.
Participants undergo the following tests and procedures:
* Insertion of a central intravenous (IV) line (plastic tube) into a large vein. The tube is used for giving the donated stem cells and antibiotics and other medicines, for transfusions of red blood cells and platelets, and for collecting blood samples.
* Preparatory chemotherapy (fludarabine, cyclophosphamide and anti-thymocyte globulin) and total body irradiation to suppress immunity and prevent rejection of the donated cells.
* Infusion of the donated stem cells and umbilical cord cells.
* Immune suppression with the drugs tacrolimus, mycophenolate mofetil and prednisone to prevent rejection of the donated cells and to prevent graft-versus-host disease (GVHD), a complication of stem cell transplants in which the donors immune cells destroy the patients healthy tissues.
The average hospital stay after stem cell transplantation is 3 to 4 weeks. Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation. Once the patient returns home, his or her referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter. Patient follow-up visits are scheduled at NIH at 1, 2, 3, 4 and 5 years after transplantation to monitor for signs of disease or post-transplantation complications, such as infection or GVHD. After 5 years, participants are offered the opportunity to enroll in NHLBIs long-term evaluation and follow-up care protocol.
Eligibility Criteria
- INCLUSION CRITERIA - RECIPIENT:
- Diagnosed with severe aplastic anemia characterized by all of the following:
- Bone marrow cellularity less than 30 percent (excluding lymphocytes)
- Transfusion dependence for platelets and/or red blood cells (RBCs)
- Neutropenia (absolute neutrophil count less than 500 cells/microL) OR for patients receiving granulocyte transfusions, absolute neutrophil count 2.5 mg/dl
- Failure to collect an adequate number of CD34+ cells (i.e. greater than or equal 2 x 10(6) CD34+ cells/kg) for transplantation from the subject s haploidentical relative.
- Presence of an active infection not adequately responding to appropriate therapy
- History of a malignant disease liable to relapse or progress within 5 years
INCLUSION CRITERIA - RELATED HAPLOIDENTICAL DONOR DONATING PURIFIED CD34 PLUS CELLS:
- HLA mismatched family donor (greater than or equal to 5/10 and less than or equal to 8/10 HLA matched (HLA-A, B, C, DR and DO loci) who is available to donate CD34+ cells.
- Ages 4-75 inclusive
- Weight greater than or equal to 15 kg.
- For adults: Ability to comprehend the investigational nature of the study and provide informed consent. For minors: Written informed consent from one parent or guardian who is not the recipient of the transplant and informed assent: The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
- If there is a suspicion of familial BMFS in the recipient, then the donor must have undergone genetic testing for genes associated with BMFS - performed at a CLIA-certified laboratory, prior to enrolling in this protocol.
EXCLUSION CRITERIA RELATED DONOR (ANY OF THE FOLLOWING):
- Pregnant or breastfeeding.
- A suitable adult haplo identical donor is available.
- Unfit to receive filgrastim (G-CSF) and undergo apheresis (history of stroke, MI, unstable angina, uncontrolled hypertension, severe heart disease or palpable spleen).
- HIV positive (Donors who are positive for HBV, HCV or HTLV I/II, T. cruzi [Chagas] may be used at the discretion of the investigator following counseling and approval from the recipient).
- Sickling hemoglobinopathies including HbSS, HbAS, HbSC. Donors with HbAS are acceptable.
- Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely and making informed consent impossible.
- Screening test positive for Chagas disease (Trypanosoma cruzi /T. cruzi/trypanosomiasis) confirmed by the Center for Disease Control (CDC).
Data sourced from ClinicalTrials.gov (NCT00604201). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.