Anti-Third Party T Lymphocytes With Nonmyeloablative Stem Cell Transplantation for Indolent Lymphoid Malignancies

This study has been terminated.
(Terminated due to slow accrual.)
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00473551
First received: May 11, 2007
Last updated: December 16, 2011
Last verified: December 2011
  Purpose

Primary Objective:

1. To determine the maximally tolerated dose of anti-third party cytolytic T-lymphocytes, defined as the dose which achieve engraftment without severe GVHD (graft-vs-host disease) at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells.

Secondary Objective:

1. Toxicity, response rate, time to progression and overall survival.


Condition Intervention Phase
Leukemia
Lymphoma
Myeloma
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Mesna
Radiation: Radiation Treatment
Procedure: Stem Cell Transplantation (SCT)
Drug: Sirolimus
Procedure: Anti-third Party Cytolytic T-lymphocytes (CTL)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Anti-Third Party T Lymphocytes With Nonmyeloablative Stem Cell Transplantation for Treatment of Indolent Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants achieving engraftment without severe Graft-versus-host disease (GVHD) [ Time Frame: Baseline to 90 days ] [ Designated as safety issue: No ]
    Number of participants who achieve engraftment without severe GVHD at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells. Engraftment recorded as first day of three (3) consecutive days that the Absolute neutrophil count (ANC) exceeds 0.5 * 109/L. Graft failure is defined as failure to reach an ANC > 0.5 * 109/L within 28 days after transplantation with detectable donor cells on chimerism analysis.

  • Maximally tolerated dose of anti-third party cytolytic T-lymphocytes [ Time Frame: Baseline to 90 days ] [ Designated as safety issue: Yes ]
    Maximally tolerated dose of anti-third party cytolytic T-lymphocytes, defined as the dose which achieve engraftment without severe GVHD at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells. Engraftment recorded as first day of three (3) consecutive days that the Absolute neutrophil count (ANC) exceeds 0.5 * 109/L. For dose-finding, "toxicity" is defined as either death or acute GVHD (aGVHD) within 90 days and "response" is defined as the event the patient is alive and engrafted at day 30.


Enrollment: 4
Study Start Date: May 2007
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

Anti-Third Party CTL (Cytolytic T-lymphocytes) with Nonmyeloablative SCT (Stem Cell Transplantation)

Rituximab 375 mg/m^2 intravenously over several hours on Day -13, followed by 1000 mg/m^2 intravenously on Days -6, 1, and 8; + Cyclophosphamide 50 mg/kg intravenously over two hours on Day -6, immediately following Fludarabine; + Fludarabine 40 mg/m^2 intravenously over 30 minutes once per day for 4 days, starting Day -6; + Radiation 2Gy Total body radiation day before transplantation + Stem Cell Transplantation + Intravenous infusion of Anti-third Party CTLs.

Drug: Rituximab
375 mg/m^2 intravenously over several hours on Day -13, followed by 1000 mg/m^2 intravenously on Days -6, 1, and 8.
Other Name: Rituxan
Drug: Cyclophosphamide
50 mg/kg intravenously over two hours on Day -6, immediately following Fludarabine.
Other Names:
  • Cytoxan®
  • Neosar®
Drug: Fludarabine
40 mg/m^2 intravenously over 30 minutes once per day for 4 days, starting Day -6.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Mesna
10 mg/kg continuous intravenous infusion for 4 hours for total of 6 doses (24 hours) following Cyclophosphamide.
Radiation: Radiation Treatment
2Gy Total body radiation day before transplantation
Other Names:
  • XRT
  • RT
  • Radiotherapy
Procedure: Stem Cell Transplantation (SCT)
Allo CD34+ Selected SCT/Infusion of stem cells.
Other Name: Nonmyeloablative Stem Cell Transplantation
Drug: Sirolimus
6 mg by mouth on day -2 followed by 2 mg daily from day -1 through day +7.
Other Name: Rapamycin
Procedure: Anti-third Party Cytolytic T-lymphocytes (CTL)
Intravenous infusion of anti-third party CTL.
Other Names:
  • Third Party T-Cells
  • Lymphocytes

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-70
  • Confirmed diagnosis of follicular lymphoma, mantle cell lymphoma, chronic lymphocyte leukemia/small lymphocytic lymphoma or multiple myeloma. Patients must have had persistent or progressive disease despite initial chemotherapy. Patients must have achieved a partial or complete response to their most recent chemotherapy.
  • Patients must have an human leukocyte antigen (HLA) matched (HLA-A, B, C DR or DQ) related donor who is seropositive against Epstein Barr virus and capable of donating peripheral blood mononuclear cells and peripheral blood progenitor cells.
  • Patient must be HLA completely mismatched for HLA class I loci (A, B and C) with the 3rd party stimulator cells. HLA-A (330301, 310102) HLA-B (5801,150101[62]) HLA-C (0302, 030301)
  • Zubrod Performance Scale (PS) of 0 or 1
  • Creatinine < 1.8 mg/dl
  • Ejection fraction >/=40%
  • Corrected Carbon Monoxide Diffusing Capacity (DLCO) >/=45% predicted
  • Serum bilirubin </=1.5 mg/dl if not due to Gilbert's syndrome

Exclusion Criteria:

  • Uncontrolled infection
  • HIV, hepatitis B surface antigen or hepatitis C seropositive
  • serum glutamic-pyruvic transaminase (SGPT) > 200 IU/ml
  • Pregnant or lactating women i.e., positive Beta human chorionic gonadotrophin (hCG) test in a woman with child bearing potential. Child bearing potential is defined as not post-menopausal for 12 months or no previous surgical sterilization.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00473551

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Richard E. Champlin, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00473551     History of Changes
Other Study ID Numbers: 2005-0682
Study First Received: May 11, 2007
Last Updated: December 16, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Chronic Lymphocytic Leukemia
Lymphoma
Myeloma
Leukemia
Anti-Third Party Cytolytic Lymphocytes
Indolent Lymphoid Malignancies
Fludarabine
Fludara
Rituximab
Rituxan
Cyclophosphamide
Cytoxan®
Neosar®
Stem Cell Transplantation
T-lymphocytes
Miltenyi CliniMACS System
Graft vs. Host Disease
GVHD
Allogenic Transplant
Sirolimus
Rapamycin

Additional relevant MeSH terms:
Neoplasms
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Cyclophosphamide
Fludarabine phosphate
Sirolimus
Everolimus
Rituximab
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 01, 2014