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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

Primary Purpose

Chronic Myeloproliferative Disorders, Leukemia, Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
peripheral blood lymphocyte therapy
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation (TBI)
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring Adult leukemia, lymphoma, myelodysplastic syndromes, plasma cell disorders

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cleveland Clinic Taussig Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

T-Cell Depletion Transplant

Arm Description

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'

Outcomes

Primary Outcome Measures

Treatment-related Mortality (TRM)
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.

Secondary Outcome Measures

The Rate of Acute Graft Versus Host Disease (GVHD)
Number of Participants With Duration of Absolute Neutropenia
Number of Participants Able to Receive T-cell Add Backs
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
number of patients that were still alive and relapse free

Full Information

First Posted
January 1, 2008
Last Updated
April 18, 2017
Sponsor
The Cleveland Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00589602
Brief Title
T-Cell Depletion, Donor Hematopoietic Stem Cell Transplant (HSCT), and T-Cell Infusions in Treating Patients With Hematologic Cancer or Other Diseases
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Why Stopped
slow accrual
Study Start Date
January 2004 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Cleveland Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Malignant Plasma Cell Neoplasms, Myelodysplastic Syndromes, Precancerous/Nonmalignant Condition, Secondary Myelofibrosis
Keywords
Adult leukemia, lymphoma, myelodysplastic syndromes, plasma cell disorders

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Allogeneic Hematopoietic Stem Cell Transplantation
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
T-Cell Depletion Transplant
Arm Type
Experimental
Arm Description
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'
Intervention Type
Procedure
Intervention Name(s)
peripheral blood lymphocyte therapy
Other Intervention Name(s)
T-cell depletion
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Description
Allogeneic Hematopoietic Stem Cell Transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Description
Peripheral blood stem cell transplantation
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation (TBI)
Intervention Description
Treatment will be delivered using 6MV photons twice daily for 3 days
Primary Outcome Measure Information:
Title
Treatment-related Mortality (TRM)
Description
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.
Time Frame
180 days after transplant
Secondary Outcome Measure Information:
Title
The Rate of Acute Graft Versus Host Disease (GVHD)
Time Frame
D+100 from transplant
Title
Number of Participants With Duration of Absolute Neutropenia
Time Frame
D+100 from transplant
Title
Number of Participants Able to Receive T-cell Add Backs
Description
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.
Time Frame
through D+100
Title
Number of Participants With Relapse-free Survival
Description
number of patients that were still alive and relapse free
Time Frame
after 7 years of follow up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian J. Bolwell, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jarek Maciejewski, MD, PhD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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