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

NCT00473551 | Terminated Phase 1

• 1 other identifier: 2005-0682
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia; Lymphoma; Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants achieving engraftment without severe Graft-versus-host disease (GVHD)

  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.

  Baseline to 90 days

• Maximally tolerated dose of anti-third party cytolytic T-lymphocytes

  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.

  Baseline to 90 days

Study Arms (1)

Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna; Radiation: Radiation Treatment; Procedure: Stem Cell Transplantation (SCT); Drug: Sirolimus; Procedure: Anti-third Party Cytolytic T-lymphocytes (CTL)

Interventions

Rituximab DRUG

375 mg/m\^2 intravenously over several hours on Day -13, followed by 1000 mg/m\^2 intravenously on Days -6, 1, and 8.

Also known as: Rituxan

Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

Cyclophosphamide DRUG

50 mg/kg intravenously over two hours on Day -6, immediately following Fludarabine.

Also known as: Cytoxan®, Neosar®

Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

Fludarabine DRUG

40 mg/m\^2 intravenously over 30 minutes once per day for 4 days, starting Day -6.

Also known as: Fludarabine Phosphate, Fludara

Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

Mesna DRUG

10 mg/kg continuous intravenous infusion for 4 hours for total of 6 doses (24 hours) following Cyclophosphamide.

Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

Radiation Treatment RADIATION

2Gy Total body radiation day before transplantation

Also known as: XRT, RT, Radiotherapy

Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

Stem Cell Transplantation (SCT) PROCEDURE

Allo CD34+ Selected SCT/Infusion of stem cells.

Also known as: Nonmyeloablative Stem Cell Transplantation

Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

Sirolimus DRUG

6 mg by mouth on day -2 followed by 2 mg daily from day -1 through day +7.

Also known as: Rapamycin

Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

Anti-third Party Cytolytic T-lymphocytes (CTL) PROCEDURE

Intravenous infusion of anti-third party CTL.

Also known as: Third Party T-Cells, Lymphocytes

Anti-Third Party T Lymphocytes + Nonmyeloablative SCT

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

U.T.M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center website

MeSH Terms

Conditions

Leukemia; Lymphoma; Neoplasms, Plasma Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Graft vs Host Disease

Interventions

Rituximab; Cyclophosphamide; fludarabine; fludarabine phosphate; Mesna; Radiotherapy; Stem Cell Transplantation; Sirolimus; Lymphocyte Count

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Therapeutics; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Leukocyte Count; Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Richard E. Champlin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2007
• First Posted: May 15, 2007
• Study Start: May 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: December 19, 2011

Record last verified: 2011-12

Locations

US (1)