Methods to Enhance the Safety and Effectiveness of Stem Cell Transplants
Peripheral Blood Stem Cell Allotransplantation for Hematological Malignancies Using a Positive Stem Cell Selection Technique for T Cell Depletion, Followed by Delayed T Cell Add-Back
2 other identifiers
interventional
116
1 country
1
Brief Summary
Bone marrow stem cell transplants (otherwise called bone marrow transplants) from healthy donors are sometimes the only means of curing hematological malignant diseases such as acute and chronic leukemias, myelodysplastic syndrome, myeloproliferative diseases and lymphomas. Before transplant the patient receives chemotherapy and radiation treatment to reduce the malignancy to low levels and to prevent rejection of the transplant. The transplant restores the blood counts to normal and replaces the patients immunity with that of the donor. The donors immune cells increase the effect of the transplant by attacking remaining malignant cells. Donor immune cells (especially those called T lymphocytes) also attack healthy non-cancerous cells and tissues of the recipient causing "graft-versus-host-disease" (GVHD). Strong GVHD reactions occurring within weeks after the transplant can be life-threatening . In this study we remove most of the T lymphocytes from the transplant to minimize the risk of GVHD. However to improve immunity against residual malignant cells and boost immunity to infections, donor T cells (stored frozen at time of transplant) are given back around 90 days after the transplant when they have a reduced risk of causing serious GVHD. Any patient between 10 and 75 years of age with acute or chronic leukemia, myelodysplastic syndrome, myeloproliferative syndromes or lymphoma, who have a family member who is a suitable stem cell donor may be eligible for this study. Candidates are screened with a medical history and various tests and examinations.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2006
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2006
CompletedFirst Submitted
Initial submission to the registry
September 19, 2006
CompletedFirst Posted
Study publicly available on registry
September 20, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2014
CompletedResults Posted
Study results publicly available
January 6, 2015
CompletedJune 16, 2021
December 1, 2014
7.6 years
September 19, 2006
December 22, 2014
May 25, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Survival and Non-relapse Mortality at Day +200 Using the Miltenyi Reagent System
Subjects with hematological malignancies receiving a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90. The subjects receiving allogeneic stem cell transplantation will have stem cell product prepared using Miltenyi CliniMacs system to determine the overall survival and non-relapse mortality at day +200.
Day 200
Secondary Outcomes (4)
Number of Participants With Relapse of Disease
Day 200
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV
100 days
Number of Participants Who Developed Limited Chronic GVHD
36 months
Number of Participants Who Develop Extensive GVHD
36 months
Study Arms (2)
T Cell Depletion Transplant Participants
EXPERIMENTALParticipants with hematological malignancies received a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion at day 90.
Stem Cell Donors
OTHERAn HLA 6/6 identical family member will be co-enrolled into this study as a stem cell donor. The stem cell collection aspect of this protocol is not investigational.
Interventions
Miltenyi Clinimax CD34 Reagent System for CD34 selection and delayed T cell depletion add back
An HLA 6/6 identical family member will be co-enrolled into this study as a stem cell donor. Stem cell Donors will receive G-CSF for stem cell mobilization. The stem cell collection aspect of this protocol is not investigational.
Eligibility Criteria
You may qualify if:
- Ages 10-75 years inclusive
- Chronic myelogenous leukemia (CML):
- Subjects under the age of 21 in chronic phase
- Subjects ages 10-75 in chronic phase who have failed treatment with imatinib, have intolerance to imatinib, or who did not receive imatinib at therapeutic doses within the first 12 months from diagnosis.
- Subjects ages 10-75 in accelerated phase or blast transformation.
- Acute lymphoblastic leukemia (ALL): any of these categories: ALL in first remission with high-risk features (presenting leukocyte count greater than 100,000/cu mm, Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia) All second or subsequent remissions, primary induction failure, partially responding or untreated relapse.
- Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21). All AML in second or subsequent remission, primary induction failure and resistant relapse
- Myelodysplastic syndromes (MDS): any of these categories - refractory anemia with transfusion dependence, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative syndromes
- Myeloproliferative disorders including atypical (Ph negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia.
- Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000 /microl) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.
- Non-Hodgkins lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments
- Multiple myeloma, Waldenstrom's macroglobulinemia, unresponsive or relapsed following standard of care treatments.
- HLA identical (6/6) related donor
- 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. Informed oral consent from minors: the process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
You may not qualify if:
- Estimated probability of surviving less than three months
- 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
- Diffusion Capacity of Lung for Carbon Monoxide (DLCO) adjusted for ventilation and hemoglobin less than 65 percent predicted
- Left ventricular ejection fraction less than 40 percent
- Aspartate Aminotransferase (AST)/Serum Glutamate Oxaloacetate Transaminase (SGOT) greater than 10 times upper limit of normal (ULN) (CTCAE grade IV v3.0)
- Bilirubin greater than 5 times upper limit of normal (ULN) (CTCAE grade IV v3.0)
- Creatinine greater than 4.5 times upper limit of normal (ULN) (CTCAE grade IV v 3.0)
- Prior allogeneic stem cell transplantation.
- Related donor, HLA identical (6/6) with recipient
- Weight greater than or equal to 18 kg
- Age greater than or equal to 2 or less than or equal to 80 years old
- 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 and informed assent: The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (7)
Appelbaum FR. Haematopoietic cell transplantation as immunotherapy. Nature. 2001 May 17;411(6835):385-9. doi: 10.1038/35077251.
PMID: 11357147BACKGROUNDArmitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. doi: 10.1056/NEJM199403243301206. No abstract available.
PMID: 8114836BACKGROUNDBalaguer H, Galmes A, Ventayol G, Bargay J, Besalduch J. Splenic rupture after granulocyte-colony-stimulating factor mobilization in a peripheral blood progenitor cell donor. Transfusion. 2004 Aug;44(8):1260-1. doi: 10.1111/j.1537-2995.2004.00413.x. No abstract available.
PMID: 15265137BACKGROUNDGiudice 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: 29674506DERIVEDMcIver ZA, Yin F, Hughes T, Battiwalla M, Ito S, Koklanaris E, Haggerty J, Hensel NF, Barrett AJ. Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival. Bone Marrow Transplant. 2013 Sep;48(9):1192-7. doi: 10.1038/bmt.2013.39. Epub 2013 Mar 25.
PMID: 23524640DERIVEDMcIver Z, Melenhorst JJ, Wu C, Grim A, Ito S, Cho I, Hensel N, Battiwalla M, Barrett AJ. Donor lymphocyte count and thymic activity predict lymphocyte recovery and outcomes after matched-sibling hematopoietic stem cell transplant. Haematologica. 2013 Mar;98(3):346-52. doi: 10.3324/haematol.2012.072991. Epub 2012 Oct 12.
PMID: 23065508DERIVEDMelenhorst JJ, Tian X, Xu D, Sandler NG, Scheinberg P, Biancotto A, Scheinberg P, McCoy JP Jr, Hensel NF, McIver Z, Douek DC, Barrett AJ. Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation. Haematologica. 2012 Jun;97(6):867-73. doi: 10.3324/haematol.2011.053363. Epub 2011 Dec 1.
PMID: 22133778DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Sara Hauffe, RN Protocol Liaison
- Organization
- NIH NHLBI OCD DIR ORIC
Study Officials
- PRINCIPAL INVESTIGATOR
Minocher M Battiwalla, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Publication Agreements
- PI is Sponsor Employee
- Yes
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 19, 2006
First Posted
September 20, 2006
Study Start
September 1, 2006
Primary Completion
April 1, 2014
Study Completion
April 1, 2014
Last Updated
June 16, 2021
Results First Posted
January 6, 2015
Record last verified: 2014-12