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
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Malignant Plasma Cell Neoplasms
Myelodysplastic Syndromes
Precancerous/Nonmalignant Condition
Secondary Myelofibrosis
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Feasibility Study of T-Cell Depletion in Allogeneic Unrelated Bone Marrow Transplantation (MUD ALLO BMT) Followed by Delayed T-Cell Infusions

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.



Enrollment: 13
Study Start Date: January 2004
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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'

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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589602

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Study Chair: Brian J. Bolwell, MD The Cleveland Clinic
Principal Investigator: Jarek Maciejewski, MD, PhD The Cleveland Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jaroslaw Maciejewski, Department Chari of Translational Hematology and Oncology Research, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT00589602     History of Changes
Other Study ID Numbers: CCF-6501, P30CA043703
Study First Received: January 1, 2008
Last Updated: October 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by The Cleveland Clinic:
Adult luekemias
lymphoma
myelodysplastic syndromes
plasma cell disorders

Additional relevant MeSH terms:
Primary Myelofibrosis
Neoplasms
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Precancerous Conditions
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Cyclophosphamide
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014