NCT00061581

Brief Summary

Bone marrow transplantation (BMT) is a risky procedure. If doctors could reduce the complications, BMT would be safer to use for a wider range of conditions. The purposes of this study are

  • to prevent graft rejection by increasing the amount of immunosuppression and by giving some lymphocytes from the donor before transplant;
  • to prevent graft-versus-host disease (GVHD) by transplanting T-cell depleted stem cells;
  • to improve the immune effect against residual leukemia by the add-back of donor lymphocytes before transplant and six or more weeks after transplant. Beyond the standard transplant protocol, study participants will undergo additional procedures. First, along with total body irradiation, patients will receive two drugs (a high dose of cyclophosphamide and fludarabine) to suppress immunity and prevent rejection of the transplant. Second, four days before the transplant, patients will be given donor lymphocytes that have been irradiated to make them incapable of causing GVHD. On the day of the transplant, patients will receive an infusion of T-cell depleted bone marrow stem cells. Finally, patients will receive two doses of add-back donor T-cells (45 and 100 days post transplant) and the immunosuppressive drug cyclosporine starting on day 44 until about six months after transplant. Study participants must be between the ages of 10 and 56 and have a family member who is a suitable stem cell donor match.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started May 2003

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

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

May 19, 2003

Completed
10 days until next milestone

First Submitted

Initial submission to the registry

May 29, 2003

Completed
Same day until next milestone

First Posted

Study publicly available on registry

May 29, 2003

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 28, 2007

Completed
9.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 14, 2017

Completed
Last Updated

September 26, 2018

Status Verified

June 14, 2017

Enrollment Period

4.6 years

First QC Date

May 29, 2003

Last Update Submit

September 25, 2018

Conditions

Acute Lymphocytic LeukemiaChronic Myeloid LeukemiaAcute Myelocytic LeukemiaMyelodysplastic SyndromesMyeloproliferative Disorders

Keywords

Chronic Myelogenous LeukemiaAcute Lymphoblastic LeukemiaAcute Myelogenous Leukemia (AML)Chronic Lymphocytic LeukemiaMyelodysplastic SyndromeNon-Hodgkin's LymphomaGraft-Versus Leukemia/MyelomaGraft-Versus-Host DiseaseCyclosporineFludarabineMyelodysplasia Syndrome

Outcome Measures

Primary Outcomes (1)

  • Acute and chronic graft-versus-host disease, transplant-related mortality (TRM), overall mortality, leukemic relapse, CMV reactivation and disease, and graft failure.

Interventions

Isolex 300i Stem Cell SelectionDEVICE

Eligibility Criteria

Age10 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Recipient
  • Ages 10-55 years inclusive (but less than 56)
  • Chronic myelogenous leukemia in chronic phase
  • A) Patients not treated with STI 571 under the age of 41 (subject to regular DSMB review).
  • B) 10-55 age limits patients in chronic phase who have failed treatment with STI-571.
  • C) 10-55 age limits patients in accelerated phase or blast transformation.
  • Acute lymphoblastic leukemia, any of these categories: Adults (greater than 18 years) 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, any of these categories: refractory anemia with transfusion dependence, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia.
  • Myeloproliferative disorders (myelofibrosis, polycythemia vera, essential thrombocythemia) in transformation to acute leukemia
  • Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000/ml) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.
  • Non-Hodgkin s lymphoma including Mantle cell lymphoma relapsing or refractory to current chemotherapy and monoclonal antibody treatment and unsuitable for autologous stem cell transplantation.
  • No major organ dysfunction precluding transplantation.
  • DLCO greater than or equal to 60% predicted.
  • Left ventricular ejection fraction: greater than or equal to 40% predicted.
  • +8 more criteria

You may not qualify if:

  • Patient pregnant
  • Age less than 10 years and 56 years or more
  • Patients with CML in chronic phase who are 41 years or over in whom STI 571 is the treatment of choice
  • ECOG performance status of 2 or more
  • Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.
  • Major anticipated illness or organ failure incompatible with survival from BMT
  • DLCO less than 60% predicted.
  • Left ventricular ejection fraction: less than 40% predicted
  • Serum creatinine greater than 3mg/dl
  • Serum bilirubin greater than 4 mg/dl
  • Transaminases greater than 3 times the upper limit of normal
  • HIV positive
  • History of other malignancies except basal cell or squamous carcinoma of the skin, positive PAP smear and subsequent negative follow up, individuals with diseases listed in eligibility criteria for this protocol, but where debility or age makes the risk of intensive myeloablative therapy unacceptable. This includes patients who have received busulfan treatment for more than 6 months continuously. These patients will be considered for a non-myeloablative allogeneic transplantation protocols.
  • Donor (any of the following)
  • Pregnant or lactating
  • +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

Location

Related Publications (5)

  • Couriel D, Canosa J, Engler H, Collins A, Dunbar C, Barrett AJ. Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis following T-depleted BMT for adults with hematological malignancies. Bone Marrow Transplant. 1996 Aug;18(2):347-53.

    PMID: 8864445BACKGROUND

  • Mavroudis D, Read E, Cottler-Fox M, Couriel D, Molldrem J, Carter C, Yu M, Dunbar C, Barrett J. CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies. Blood. 1996 Oct 15;88(8):3223-9.

    PMID: 8874224BACKGROUND

  • Mavroudis DA, Read EJ, Molldrem J, Raptis A, Plante M, Carter CS, Phang S, Dunbar CE, Barrett AJ. T cell-depleted granulocyte colony-stimulating factor (G-CSF) modified allogenic bone marrow transplantation for hematological malignancy improves graft CD34+ cell content but is associated with delayed pancytopenia. Bone Marrow Transplant. 1998 Mar;21(5):431-40. doi: 10.1038/sj.bmt.1701120.

    PMID: 9535034BACKGROUND

  • McIver 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: 23524640DERIVED

  • McIver 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: 23065508DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, Myeloid, AcuteMyelodysplastic SyndromesMyeloproliferative DisordersLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Non-HodgkinNeoplasms, Plasma CellGraft vs Host Disease

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, MyeloidBone Marrow DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, B-CellLymphoma

Study Officials

  • A. John Barrett, M.D.

    National Heart, Lung, and Blood Institute (NHLBI)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH

Study Record Dates

First Submitted

May 29, 2003

First Posted

May 29, 2003

Study Start

May 19, 2003

Primary Completion

December 28, 2007

Study Completion

June 14, 2017

Last Updated

September 26, 2018

Record last verified: 2017-06-14

Locations

US(1)