T-Cell Depletion, Donor HSCT, and T-Cell Infusions in Treating Patients With Hematologic Cancer or Other Diseases (6501)
This study is ongoing, but not recruiting participants.
Sponsor:
The Cleveland Clinic
Collaborator:
Information provided by:
The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT00589602
First received: January 1, 2008
Last updated: February 14, 2011
Last verified: February 2011
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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 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: | Allocation: Non-Randomized 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: TRM ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- The rate and severity of acute GVHD [ Time Frame: Relapse and survival ] [ Designated as safety issue: Yes ]
- Duration of absolute neutropenia [ Time Frame: Relapse and survival ] [ Designated as safety issue: Yes ]
- Ability to receive T-cell add backs [ Time Frame: Relapse and Survival ] [ Designated as safety issue: No ]
- Relapse and relapse-free survival [ Time Frame: Relapse and survival ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 36 |
| Study Start Date: | January 2004 |
| Estimated Primary Completion Date: | December 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| No Intervention: Transplant Related Mortality |
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
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 |
More Information
Additional Information:
No publications provided
| Responsible Party: | Brian James Bolwell, Cleveland Clinic Taussig Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00589602 History of Changes |
| Other Study ID Numbers: | CASE-CCF-6501, P30CA043703, CASE-CCF-6501 |
| Study First Received: | January 1, 2008 |
| Last Updated: | February 14, 2011 |
| Health Authority: | United States: Federal Government |
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 October 17, 2012
