Stem Cell Transplant Using Peripheral and Cord Blood Stem Cells to Treat Severe Aplastic Anemia and Myelodysplastic Syndrome

NCT00604201 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 08004608-H-0046
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myelodysplastic Syndrome (MDS) With Refractory Anemia (RA); Severe Aplastic Anemia (SAA)

Keywords

Nonmyeloablative; Haploidentical; Umbilical Cord Blood; SAA; Severe Aplastic Anemia; Myelodysplastic Syndrome; MDS

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Engrafted by Day 42

  Participants who reached engraftment by day 42 (±3 days) defined as an absolute neutrophil count (ANC) of U\> U500 cells/µl

  42 days

Secondary Outcomes (12)

• Number of Participants Who Developed Chronic GVHD

  5 years

• Number of Participants Who Developed Acute GVHD

  100 days

• Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 100

  100 days

• Number of Participants Who Experienced Treatment Related Mortality (TRM) Day 200

  200 days

• Number of Participants Who Had ANC Recovery at Day 22

  22 days

Study Arms (1)

Co-infusion of UCB and Haploidentical CD34+ cells

EXPERIMENTAL

Stem cell recipients received co-infusion of unrelated umbilical cord blood (UCB) and haploidentical CD34+ cells from a related donor following non-myeloablative conditioning for neutropenic patients with severe aplastic anemia (SAA) or myelodysplastic syndrome (MDS) with refractory anemia (RA)

Biological: Umbilical Cord Blood

Interventions

Umbilical Cord Blood BIOLOGICAL

unrelated umbilical cord blood will be co-infused with haploidentical CD34-selected cells from a related donor for treatment of severe aplastic anemia and myelodysplastic syndrome.

Co-infusion of UCB and Haploidentical CD34+ cells

Eligibility Criteria

• Age: 4 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \< 500 cells/microL before beginning granulocyte transfusions\].)
• Diagnosed with myelodysplastic syndrome characterized by refractory anemia OR refractory anemia with ringed sideroblasts (RARS and at least one of the following:
• Neutropenia \[(absolute neutrophil count \< 500 cells/microL) OR for patients receiving granulocyte transfusions, absolute neutrophil count \< 500 cells/microL before beginning granulocyte transfusions\]) and history of 1 or more opportunistic infections related to neutropenia. OR
• History of severe aplastic anemia transformed to MDS
• Intolerance of or failure to respond standard immunosuppressive therapy.
• Availability of at least one HLA-haploidentical (i.e. greater than or equal to 5/10 and less than or equal to 8/10 HLA match) related donor (HLA-A, B, C, DR, and DO loci) who is available to donate CD34+ cells (4-75 years old).
• Availability of at least one 4/6 HLA-matched (HLA-A, B, and DR loci) cord blood unit from the National Marrow Donor Program (NMDP). The cord blood unit must contain a minimum total nucleated cells (TNC) (prior to thawing) of at least 1.5 x 10(7) cells per kilogram of recipient body weight with the following exception: if the minimum criterion of TNC is not met the cord unit must contain at least 1.7 x 10(5) CD34 plus cells/kg (prior to thawing).
• Ages 4-55 years inclusive.
• Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects aged 4-17 years with formal consent being obtained from parents or legal guardian.
• Telomere Length Testing
• In patients where a suspicion for a familial bone marrow failure syndromes (BMFS) exists, TERC and TERT mutation testing will be performed on protocol 04-H-0012 or performed elsewhere prior to enrolling on 04-H-0012.

You may not qualify if:

• Availability of an HLA identical or 9/10 HLA matched(HLA A, B, C, DR, and DO loci-relative to serve as a stem cell donor.
• The patient is deemed to be a candidate for a 6/6 HLA matched unrelated stem cell transplant (availability of a donor and resources required for such a transplant).
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more.
• Major anticipated illness or organ failure incompatible with survival from transplant
• Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and making informed consent impossible.
• Positive pregnancy test for women of childbearing age.
• HIV positive
• Diagnosis of Fanconi anemia (by chromosome breakage study).
• Diffusion capacity of carbon monoxide (DLCO) less than 40 percent using DLCO corrected for Hgb or lung volumes (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 less than 40 percent (evaluated by ECHO)
• Transaminases greater than 5x upper limit of normal (when transaminases are elevated, the subject may be excluded at the discretion of the PI).
• Serum bilirubin greater than 4 mg/dl
• Creatinine clearance less than 50 cc/min by 24 hr urine collection (adjusted for body surface area, i.e.50 ml/min/1.73m(2))
• Serum creatinine \> 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.

  PMID: 7780125 BACKGROUND

• Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. doi: 10.1056/NEJM199705083361906. No abstract available.

  PMID: 9134878 BACKGROUND

• Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65. doi: 10.1056/NEJM198501313120501.

  PMID: 2981406 BACKGROUND

• Giudice V, Wu Z, Kajigaya S, Fernandez Ibanez MDP, Rios O, Cheung F, Ito S, Young NS. Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes. Cytokine. 2019 Jan;113:462-465. doi: 10.1016/j.cyto.2018.06.025. Epub 2018 Jun 27.

  PMID: 29958797 DERIVED

• Giudice V, Banaszak LG, Gutierrez-Rodrigues F, Kajigaya S, Panjwani R, Ibanez MDPF, Rios O, Bleck CK, Stempinski ES, Raffo DQ, Townsley DM, Young NS. Circulating exosomal microRNAs in acquired aplastic anemia and myelodysplastic syndromes. Haematologica. 2018 Jul;103(7):1150-1159. doi: 10.3324/haematol.2017.182824. Epub 2018 Apr 19.

  PMID: 29674506 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia, Aplastic

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia; Bone Marrow Failure Disorders

Results Point of Contact

• Title: Childs, William
• Organization: National Heart Lung and Blood Institute

childsr@nhlbi.nih.gov

+1 301 451 7128

Study Officials

• Richard W Childs, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2008
• First Posted: January 30, 2008
• Study Start: May 21, 2008
• Primary Completion: October 25, 2016
• Study Completion: September 14, 2021
• Last Updated: January 5, 2022
• Results First Posted: July 31, 2020

Record last verified: 2021-12

Locations

US (1)