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T-Cell Depletion, Donor HSCT, and T-Cell Infusions in Treating Patients With Hematologic Cancer or Other Diseases

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jaroslaw Maciejewski, The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT00589602
First received: January 1, 2008
Last updated: October 18, 2013
Last verified: October 2013

January 1, 2008
October 18, 2013
January 2004
December 2015   (final data collection date for primary outcome measure)
Treatment-related mortality (TRM) [ Time Frame: Although safety will be continuously monitored, we will include two formal safety checks. ] [ Designated as safety issue: Yes ]

Although safety will be continuously monitored, we will include two formal safety checks.

After the first 10 patients are enrolled, accrual will halt temporarily until all 10 patients have been followed for 45 days post-transplant so that graft failure can be assessed. If 4 or more patients experience graft failure by day 45, the study will be terminated. Otherwise, the study will continue. Assuming the study continues, chimerism will continue to be monitored. If, in the first 10 patients who survive >180 days, "If chimerism studies of the first ten patients surviving 180 days reveal that 4 or more patients are not fully T cell and buffy coat chimeric then the study will be terminated.

Treatment-related mortality (TRM) [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00589602 on ClinicalTrials.gov Archive Site
  • The rate and severity of acute GVHD [ Time Frame: Although safety will be continuously monitored, we will include two formal safety checks. ] [ Designated as safety issue: Yes ]

    Although safety will be continuously monitored, we will include two formal safety checks.

    After the first 10 patients are enrolled, accrual will halt temporarily until all 10 patients have been followed for 45 days post-transplant so that graft failure can be assessed. If 4 or more patients experience graft failure by day 45, the study will be terminated. Otherwise, the study will continue. Assuming the study continues, chimerism will continue to be monitored. If, in the first 10 patients who survive >180 days, "If chimerism studies of the first ten patients surviving 180 days reveal that 4 or more patients are not fully T cell and buffy coat chimeric then the study will be terminated.

  • Duration of absolute neutropenia [ Time Frame: Although safety will be continuously monitored, we will include two formal safety checks. ] [ Designated as safety issue: Yes ]

    Although safety will be continuously monitored, we will include two formal safety checks.

    After the first 10 patients are enrolled, accrual will halt temporarily until all 10 patients have been followed for 45 days post-transplant so that graft failure can be assessed. If 4 or more patients experience graft failure by day 45, the study will be terminated. Otherwise, the study will continue. Assuming the study continues, chimerism will continue to be monitored. If, in the first 10 patients who survive >180 days, "If chimerism studies of the first ten patients surviving 180 days reveal that 4 or more patients are not fully T cell and buffy coat chimeric then the study will be terminated.

  • Ability to receive T-cell add backs [ Time Frame: Although safety will be continuously monitored, we will include two formal safety checks. ] [ Designated as safety issue: No ]

    Although safety will be continuously monitored, we will include two formal safety checks.

    After the first 10 patients are enrolled, accrual will halt temporarily until all 10 patients have been followed for 45 days post-transplant so that graft failure can be assessed. If 4 or more patients experience graft failure by day 45, the study will be terminated. Otherwise, the study will continue. Assuming the study continues, chimerism will continue to be monitored. If, in the first 10 patients who survive >180 days, "If chimerism studies of the first ten patients surviving 180 days reveal that 4 or more patients are not fully T cell and buffy coat chimeric then the study will be terminated.

  • Relapse and relapse-free survival [ Time Frame: Although safety will be continuously monitored, we will include two formal safety checks. ] [ Designated as safety issue: No ]

    Although safety will be continuously monitored, we will include two formal safety checks.

    After the first 10 patients are enrolled, accrual will halt temporarily until all 10 patients have been followed for 45 days post-transplant so that graft failure can be assessed. If 4 or more patients experience graft failure by day 45, the study will be terminated. Otherwise, the study will continue. Assuming the study continues, chimerism will continue to be monitored. If, in the first 10 patients who survive >180 days, "If chimerism studies of the first ten patients surviving 180 days reveal that 4 or more patients are not fully T cell and buffy coat chimeric then the study will be terminated.

  • The rate and severity of acute GVHD [ Designated as safety issue: Yes ]
  • Duration of absolute neutropenia [ Designated as safety issue: Yes ]
  • Ability to receive T-cell add backs [ Designated as safety issue: No ]
  • Relapse and relapse-free survival [ Designated as safety issue: No ]
Not Provided
Not Provided
 
T-Cell Depletion, Donor 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 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 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
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Malignant Plasma Cell Neoplasms
  • Myelodysplastic Syndromes
  • Precancerous/Nonmalignant Condition
  • Secondary Myelofibrosis
  • Biological: peripheral blood lymphocyte therapy
    T-cell depletion
    Other Name: T-cell depletion
  • Drug: cyclophosphamide
    T-cell depletion
    Other Name: T-cell depletion
  • Drug: tacrolimus
    T-cell depletion
    Other Name: T-cell depletion
  • Procedure: allogeneic hematopoietic stem cell transplantation
    T-cell depletion
    Other Name: T-cell depletion
  • Procedure: peripheral blood stem cell transplantation
    T-cell depletion
    Other Name: T-cell depletion
  • Radiation: total-body irradiation
    T-cell depletion
    Other Name: T-cell depletion
Experimental: T-Cell Depletion Transplant

Our protocol is designed to attempt to improve the current results of MUD allo 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:
  • Biological: peripheral blood lymphocyte therapy
  • Drug: cyclophosphamide
  • Drug: tacrolimus
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: total-body irradiation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
13
Not Provided
December 2015   (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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00589602
CCF-6501, P30CA043703
Yes
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
October 2013

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