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T-Cell Depletion, Donor Hematopoietic Stem Cell Transplant (HSCT), and T-Cell Infusions in Treating Patients With Hematologic Cancer or Other Diseases

This study has been terminated.
(slow accrual)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jaroslaw Maciejewski, The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT00589602
First received: January 1, 2008
Last updated: April 18, 2017
Last verified: April 2017
January 1, 2008
April 18, 2017
January 2004
August 2009   (Final data collection date for primary outcome measure)
Treatment-related Mortality (TRM) [ Time Frame: 180 days after transplant ]
The complication rate in matched unrelated donor (MUD) allogeneic bone marrow transplant (allo BMT) is known to be high. Graft failure and severe graft versus host disease (GvHD) are the most significant contributors to treatment related mortality (TRM). This treatment regimen will be considered unacceptable if the number of patients that experience TRM is 55% or greater, and effective if TRM is 33% or less.
Treatment-related Mortality (TRM)
Complete list of historical versions of study NCT00589602 on ClinicalTrials.gov Archive Site
  • The Rate of Acute Graft Versus Host Disease (GVHD) [ Time Frame: D+100 from transplant ]
  • Number of Participants With Duration of Absolute Neutropenia [ Time Frame: D+100 from transplant ]
  • Number of Participants Able to Receive T-cell Add Backs [ Time Frame: through D+100 ]
    Patients receive defined doses of donor T cells by IV infusion on days 45 and 100, in absence of active graft-versus-host disease (GVHD) requiring steroids.
  • Number of Participants With Relapse-free Survival [ Time Frame: after 7 years of follow up ]
    number of patients that were still alive and relapse free
  • The rate and severity of acute GVHD
  • Duration of absolute neutropenia
  • Ability to receive T-cell add backs
  • Relapse and relapse-free survival
Not Provided
Not Provided
 
T-Cell Depletion, Donor Hematopoietic Stem Cell Transplant (HSCT), and T-Cell Infusions in Treating Patients With Hematologic Cancer or Other Diseases
Phase II Feasibility Study of T-Cell Depletion in Allogeneic Unrelated Bone Marrow Transplantation (MUD ALLO BMT) Followed by Delayed T-Cell Infusions

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help destroy any remaining cancer cells (graft-versus-tumor effect).

PURPOSE: This phase II trial is studying T-cell depletion in donor stem cell transplant followed by delayed T cell infusions in treating patients with hematologic cancer or other disease.

OBJECTIVES:

Primary

  • Determine if T-cell depletion of a peripheral blood progenitor cell (PBPC) graft followed by delayed add-backs of defined doses of donor lymphocytes decreases the rate of graft-versus-host disease and its complications in matched unrelated donor (MUD) allogeneic peripheral blood progenitor cell (PBPC) transplantation in patients with hematologic cancers or other diseases.
  • Determine whether targeted T-cell dosages in the PBPC graft can be achieved in these patients by positive CD34+ selection using the Baxter Inc. Isolex 300i v. 2.5.
  • Determine the effects of T-cell depletion on the rate of engraftment in these patients.
  • Develop a matched unrelated donor (MUD) allogeneic transplantation regimen that will decrease overall treatment-related mortality in these patients.

OUTLINE: This is a non-randomized study.

  • Myeloablative preparative regimen: Patients receive cyclophosphamide IV once daily on days -5 and -4 followed by total body irradiation twice daily on days -3, -2, and -1. Patients also receive tacrolimus on day -1 administered by continuous IV infusion over 24 hours.
  • Peripheral blood progenitor cell graft transplantation: Patients receive T-cell depleted, peripheral blood progenitor cells (PBPC) by IV infusion on day 0. Beginning 1 day after completion of the PBPC infusion, patients receive filgrastim (G-CSF) subcutaneously once daily until blood counts recover.
  • Post transplantation T cell add-backs: Patients receive defined doses of donor T cells by IV infusion on days 45 and 100, in the absence of active graft-versus-host disease (GVHD) requiring steroids*.

NOTE: *A T cell add-back may be given in the presence of GVHD, if the investigator considers the risk from relapse or overwhelming viral infection to outweigh the risk of exacerbating GVHD.

Patients will be followed periodically for relapse and survival.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Intervention Model Description:
Allogeneic Hematopoietic Stem Cell Transplantation
Masking: No masking
Primary Purpose: Treatment
  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Malignant Plasma Cell Neoplasms
  • Myelodysplastic Syndromes
  • Precancerous/Nonmalignant Condition
  • Secondary Myelofibrosis
  • Procedure: peripheral blood lymphocyte therapy
    T-cell depletion will be accomplished using CD34 selection with the Baxter Isolex 300i v. 2.5 device. The desirable T-cell dose will be >0.5 x 105 but <1.0 x 105 CD3+ cells per kg. The targeted CD34 cell dose will be >2 x 106 cells/kg.
    Other Name: T-cell depletion
  • Procedure: allogeneic hematopoietic stem cell transplantation
    Allogeneic Hematopoietic Stem Cell Transplantation
  • Procedure: peripheral blood stem cell transplantation
    Peripheral blood stem cell transplantation
  • Radiation: total-body irradiation (TBI)
    Treatment will be delivered using 6MV photons twice daily for 3 days
Experimental: T-Cell Depletion Transplant

Our protocol is designed to attempt to improve the current results of matched unrelated donor (MUD) allo bone marrow transplant (BMT) and will be a major step towards the introduction and refinement of graft engineering. Our approach will address in a rational fashion all major technical and clinical aspects of MUD allo BMT.

Peripheral blood lymphocyte therapy; cyclophosphamide, tacrolimus, peripheral blood stem cell transplantation; total-body irradiation; 'allogeneic hematopoietic stem cell transplantation'

Interventions:
  • Procedure: peripheral blood lymphocyte therapy
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: total-body irradiation (TBI)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
13
December 2014
August 2009   (Final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of any of the following hematologic cancers or other diseases:

    • Acute myelogenous leukemia

      • Relapsed or refractory disease with poor-risk cytogenetics
    • Acute lymphoblastic leukemia

      • Relapsed or refractory disease with poor-risk cytogenetics
    • Chronic myelogenous leukemia

      • Persistent disease after at least 6 months of treatment with imatinib mesylate (Gleevec)
    • Myelodysplasia, meeting 1 of the following criteria:

      • French-American-British Classification of refractory anemia with excess blasts (RAEB) or RAEB with transformation
      • International Prognostic Scoring System score > 2
    • Lymphoid malignancies, including non-Hodgkin lymphoma, Hodgkin disease, chronic lymphocytic leukemia, and prolymphocytic leukemia

      • Relapsed or refractory disease after at least 1 prior therapy
    • Myelofibrosis

      • Transfusion dependent (RBC's, platelets, or both)
    • Paroxysmal nocturnal hemoglobinuria (transfusion dependent)
    • Myeloproliferative disorder
    • Eosinophilic leukemia
    • Severe aplastic anemia

      • Corrected reticulocyte count < 1%
      • Platelet count < 30,000/mm³ (untransfused)
      • Bone marrow biopsy with < 15% cellularity
    • Plasma cell leukemia
  • No essential thrombocytopenia or polycythemia vera
  • No matched related donor available
  • Must have an 8/8 or 7/8 serologic HLA matched unrelated donor available

PATIENT CHARACTERISTICS:

  • Cardiac ejection fraction ≥ 45% (if < 45%, then cardiac consult required)
  • Not pregnant or nursing
  • Negative pregnancy test
  • FEV_1 and DLCO ≥ 45% predicted
  • Creatinine < 2.0 mg/dL
  • Bilirubin < 2.0 mg/dL
  • HIV negative

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior allogeneic bone marrow transplantation
  • No concurrent administration of steroids with T-cell add-backs

INCLUSION CRITERIA:

  • Patient actual weight must not be greater than 1.5x their ideal body weight
  • Cardiac ejection fraction >45%. If less than 45%, a Cardiac consult will be obtained.
  • A suitably matched unrelated donor that is at least a 7 out of 8 HLA serologic match.
  • Patient is not pregnant.
  • FEV 1 and DLCO > 45% predicted on pulmonary function testing.
  • Serum creatinine <2.0 mg/dl, serum bilirubin <2.0 mg/dl.
  • Patient and donor are HIV negative.
  • Diagnosis of one of the following diseases
  • Acute myelogenous leukemia
  • Relapsed disease,
  • Refractory disease, or
  • With poor-risk cytogenetics
  • Acute lymphoblastic leukemia
  • Relapsed disease,
  • Refractory disease, or
  • With poor-risk cytogenetics
  • Chronic myelogenous leukemia
  • Persistent disease after at least 6 months of treatment with Imatinib Mesylate (Gleevec)
  • Myelodysplasia
  • FAB Classification of RAEB or RAEB-T -Or-
  • IPSS score >2
  • Lymphoid malignancies, including non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia and prolymphocytic leukemia
  • Relapsed or refractory disease after at least 1 prior therapy
  • Myelofibrosis
  • Transfusion dependence (RBC's, platelets, or both)
  • Paroxysmal Nocturnal Hemoglobinuria (PNH)
  • Transfusion dependent
  • Myeloproliferative Disorder
  • Eosinophilic Leukemia
  • Severe aplastic anemia (<1% corrected reticulocyte count, <30,000 untransfused platelet count, bone marrow biopsy with <15% cellularity)
  • Plasma cell leukemia
  • Patients with ET or PV will not be candidates unless their disease has transformed to end stage myelofibrosis or acute leukemia, for which eligibility criteria for myelofibrosis or acute leukemia would apply.
  • Patient must signed written informed consent.

EXCLUSION CRITERIA:

  • Inability to give informed consent
  • Absence of any of the above mentioned medical conditions
  • Availability of matched-related donor
  • History of prior allogeneic BMT
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00589602
CCF-6501
P30CA043703 ( US NIH Grant/Contract Award Number )
Yes
Not Provided
No
Not Provided
Jaroslaw Maciejewski, The Cleveland Clinic
The Cleveland Clinic
National Cancer Institute (NCI)
Study Chair: Brian J. Bolwell, MD The Cleveland Clinic
Principal Investigator: Jarek Maciejewski, MD, PhD The Cleveland Clinic
The Cleveland Clinic
April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP