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

NCT ID: NCT00589602

Last Updated: 2017-05-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-01-31

Study Completion Date

2014-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Allogeneic Hematopoietic Stem Cell Transplantation
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

T-Cell Depletion Transplant

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'

Group Type EXPERIMENTAL

peripheral blood lymphocyte therapy

Intervention Type PROCEDURE

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.

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

Allogeneic Hematopoietic Stem Cell Transplantation

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Peripheral blood stem cell transplantation

total-body irradiation (TBI)

Intervention Type RADIATION

Treatment will be delivered using 6MV photons twice daily for 3 days

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

peripheral blood lymphocyte therapy

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

allogeneic hematopoietic stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Peripheral blood stem cell transplantation

Intervention Type PROCEDURE

total-body irradiation (TBI)

Treatment will be delivered using 6MV photons twice daily for 3 days

Intervention Type RADIATION

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

T-cell depletion

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Jaroslaw Maciejewski

Department Chair of Translational Hematology and Oncology Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Brian J. Bolwell, MD

Role: STUDY_CHAIR

The Cleveland Clinic

Jarek Maciejewski, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CCF-6501

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.