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

NCT00589602 | Terminated Phase 2 Results DMC

• 2 other identifiers: CCF-6501P30CA043703
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  180 days after transplant

Secondary Outcomes (4)

• The Rate of Acute Graft Versus Host Disease (GVHD)

  D+100 from transplant

• Number of Participants With Duration of Absolute Neutropenia

  D+100 from transplant

• Number of Participants Able to Receive T-cell Add Backs

  through D+100

• Number of Participants With Relapse-free Survival

  after 7 years of follow up

Study Arms (1)

T-Cell Depletion Transplant

EXPERIMENTAL

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'

Procedure: peripheral blood lymphocyte therapy; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation (TBI)

Interventions

peripheral blood lymphocyte therapy 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.

Also known as: T-cell depletion

T-Cell Depletion Transplant

allogeneic hematopoietic stem cell transplantation PROCEDURE

Allogeneic Hematopoietic Stem Cell Transplantation

T-Cell Depletion Transplant

peripheral blood stem cell transplantation PROCEDURE

Peripheral blood stem cell transplantation

T-Cell Depletion Transplant

total-body irradiation (TBI) RADIATION

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

T-Cell Depletion Transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Inability to give informed consent
• Absence of any of the above mentioned medical conditions
• Availability of matched-related donor
• History of prior allogeneic BMT

Sponsors & Collaborators

• The Cleveland Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma; Myelodysplastic Syndromes; Precancerous Conditions

Interventions

Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Jarek Maciejewski, MD
• Organization: Cleveland Clinic

maciejj@ccf.org

216-445-5962

Study Officials

• Brian J. Bolwell, MD

  The Cleveland Clinic

  STUDY CHAIR

• Jarek Maciejewski, MD, PhD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department Chair of Translational Hematology and Oncology Research

Model Details: Allogeneic Hematopoietic Stem Cell Transplantation

Study Record Dates

• First Submitted: January 1, 2008
• First Posted: January 9, 2008
• Study Start: January 1, 2004
• Primary Completion: August 1, 2009
• Study Completion: December 1, 2014
• Last Updated: May 30, 2017
• Results First Posted: May 30, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)