Donor T Cells in Treating Patients With High-Risk Hematologic Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant

Lymphoma Clinical Trial

Official title:

Phase I-II Dose Escalation Study of CD4+CD25+ Cells in Adult Patients Undergoing HLA-Identical Sibling Donor Peripheral Blood Progenitor Cell Transplantation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00725062
• Other study ID #: 2004LS034
• Secondary ID: MT2004-03
• Status: Terminated
• Phase: Phase 1
• First received: July 29, 2008
• Last updated: November 27, 2017
• Start date: June 2008
• Est. completion date: April 2010

Study information

• Verified date: November 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: A donor peripheral stem cell transplant helps stop the growth of cancer cells. When the healthy 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. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of donor T cells may helps stop the patient's immune system from rejecting the donor's stem cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of donor T cells in treating patients with high-risk hematologic cancer who are undergoing donor peripheral blood stem cell transplant.

Note: Only Phase I portion of study was performed. Due to slow accrual, study was closed before Phase II portion of study.

Description:

OBJECTIVES:

Primary

• To determine the maximum tolerated dose (MTD) of CD4+/CD25+ cells that can be safely administered to patients undergoing HLA-identical sibling donor Peripheral Blood Progenitor Cell (PBPC) transplantation.

• To determine whether CD4+ and CD25+ cells can be safely administered to patients with high-risk hematologic malignancies undergoing HLA-identical sibling donor PBPC transplantation.

Secondary

• To determine the incidence of grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, relapse, and survival after administration of CD4+ and CD25+ regulatory T cells in these patients.

OUTLINE: This is a dose-escalation study of CD4+ and CD25+ donor regulatory T cells followed by a phase II study. All patients receive myeloablative preparative therapy and GVHD prophylaxis as per University of Minnesota protocol UMN-MT2001-02 or UMN-MT2001-10.

• First allogeneic peripheral blood progenitor cell (PBPC) infusion: Patients receive unmobilized, culture-expanded, CD4- and CD25-positive donor regulatory T cells IV over 15-60 minutes at the assigned dose on day -2.

• Second allogeneic PBPC infusion: Patients undergo matched-sibling donor PBPC transplantation IV on day 0.

Patients undergo blood sample collection prior to commencement of preparative therapy and then at day 100, 6 months, and 1 year after PBPC transplantation. Samples are analyzed for immune reconstitution by immunophenotyping and functional analyses.

After completion of study therapy, patients are followed for up to 1 year.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Diagnosis of a high-risk hematologic malignancy, including any of the following:

• Acute lymphocytic leukemia

• Acute myelocytic leukemia

• Chronic myelogenous leukemia

• Myelodysplastic syndrome

• Non-Hodgkin lymphoma

• Multiple myeloma

• Meet eligibility criteria and co-enrolled in one of the following University of Minnesota protocols:

• MT2001-02 consisting of myeloablative prep (cyclophosphamide and total body irradiation) followed by HLA-identical sibling peripheral blood progenitor cells (PBPC) transplantation

• MT2001-10 consisting of nonmyeloablative prep (cyclophosphamide, fludarabine and total body irradiation) followed by HLA-identical sibling PBPC transplantation

• Voluntarily written informed consent

• Must have an HLA-identical sibling donor available, meeting the following criteria:

• 12 to 75 years of age, >40 kg body weight and in good health

• Matched to recipient for HLA-A, B,DRB1 identical sibling match to recipient

• Must be able and willing to have a separate apheresis collection performed on day -21 for the purposes of this study (in addition to the apheresis required for the transplant protocol)

• Human immunodeficiency virus nucleic acid testing (HIV-NAT) negative, Human T-lymphotropic virus 1 (HTLV-1), HTLV-2 negative, hepatitic B and C negative

Exclusion Criteria:

• Not pregnant or nursing

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Neoplasms, Plasma Cell
• Plasmacytoma
• Preleukemia
• Syndrome

Intervention

Biological:
• CD4+CD25+ regulatory T cells
Cohort 1 will receive 3 x 10^6 CD4+CD25+ cells/kg, Cohort 2 will receive 1 x 10^7 CD4+CD25+ cells/kg, Cohort 3 will receive 3 x 10^7 CD4+CD25 cells/kg

Procedure:
• allogeneic hematopoietic stem cell transplantation
Occurs on Day 0 of study - HLA-identical sibling donor peripheral blood progenitor cell (PBPC) transplantation

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of CD4+CD25+ cells/kg (phase I)		Day 0 (48 hours post infusion)
Primary	Incidence of grade 3-5 infusional toxicity (phase II)		Day 0 (48 hours post infusion)
Secondary	Cumulative incidence of grade II-IV acute graft-versus-host-disease (GVHD)		Day 100 Post Infusion
Secondary	Incidence of chronic graft-versus-host disease (GVHD)		Month 6 Post Infusion
Secondary	Incidence of Relapse		Month 6 Post Infusion
Secondary	Overall Survival		Day 100 and 1 Year Post Infusion
Secondary	Disease-free survival		Day 100 and 1 Year Post Infusion