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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00589602
• Other study ID #: CCF-6501
• Secondary ID: P30CA043703
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 1, 2008
• Last updated: October 18, 2013
• Start date: January 2004

Study information

• Verified date: October 2013
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 13
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Malignant Plasma Cell Neoplasms
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Plasmacytoma
• Precancerous Conditions
• Precancerous/Nonmalignant Condition
• Preleukemia
• Secondary Myelofibrosis

Intervention

Biological:
• peripheral blood lymphocyte therapy
T-cell depletion

Drug:
• cyclophosphamide
T-cell depletion
• tacrolimus
T-cell depletion

Procedure:
• allogeneic hematopoietic stem cell transplantation
T-cell depletion
• peripheral blood stem cell transplantation
T-cell depletion

Radiation:
• total-body irradiation
T-cell depletion

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
The Cleveland Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related mortality (TRM)	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.	Although safety will be continuously monitored, we will include two formal safety checks.	Yes
Secondary	The rate and severity of acute GVHD	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.	Although safety will be continuously monitored, we will include two formal safety checks.	Yes
Secondary	Duration of absolute neutropenia	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.	Although safety will be continuously monitored, we will include two formal safety checks.	Yes
Secondary	Ability to receive T-cell add backs	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.	Although safety will be continuously monitored, we will include two formal safety checks.	No
Secondary	Relapse and relapse-free survival	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.	Although safety will be continuously monitored, we will include two formal safety checks.	No