Infusion of Expanded Cord Blood T Cells - Full Text View

Purpose

The goal of this clinical research study is to learn if treating umbilical cord blood with growth factors before a transplant can help to improve the body's ability to accept the cord blood transplants.

Condition	Intervention	Phase
Stem Cell Transplantation Leukemia Lymphoma Pediatric Disorders	Radiation: Total Body Irradiation (TBI) Drug: Melphalan Drug: Thiotepa Drug: Fludarabine Drug: Rituximab Drug: Etoposide Drug: Anti-thymocyte globulin (ATG) Drug: Mycophenolate Mofetil (MMF) Drug: Tacrolimus Procedure: Cord Blood Infusion Drug: G-CSF Procedure: Ex vivo expanded T cell Infusion	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Infusion of Expanded Cord Blood T Cells Following Cord Blood Transplantation

Resource links provided by NLM:

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

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) [ Time Frame: Days 14 to 100 ] [ Designated as safety issue: Yes ]

Enrollment:	0
Study Start Date:	September 2009
Study Completion Date:	September 2011
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Regimen 1: No TBI High Dose Chemotherapy without Total Body Irradiation (TBI)	Drug: Melphalan 140 mg/m^2 by vein over 30 minutes as a single dose on Day -8 Other Name: Alkeran Drug: Thiotepa 10 mg/kg by vein over 4 hours as a single dose on Day -7 Drug: Fludarabine 40 mg/m^2 by vein over about 30 minutes 1 time each day on Days -6 through -3. Other Names: Fludara Fludarabine Phosphate Drug: Rituximab Regimen 1: 375 mg/m^2 may be given by vein over 4 - 6 hours on Day -9 if needed Regimen 2: 375 mg/m^2 may be given by vein over 4 - 6 hours on Day -8 if needed Other Name: Rituxan Drug: Anti-thymocyte globulin (ATG) Regimen 1: 1.25 and 1.75 mg/kg by vein over 4-6 hours on the Days -4 and -3. Regimen 2: 0.5, 1.0 and 1.5 mg/kg by vein over 4-6 hours on respective Days -3, -2, and -1. Other Name: Thymoglublin Drug: Mycophenolate Mofetil (MMF) 15 mg/kg pills twice a day starting on day -3, and continued until Day 100+ after transplant (1 gram may be given by vein if necessary). Other Name: CellCept Drug: Tacrolimus 0.03 mg/kg by vein Day -2 as 24 hour continuous infusion for several weeks. After stem cell transplant, tacrolimus given by mouth 2 times a day for up to 6 months. Other Names: FK506 Prograf Procedure: Cord Blood Infusion Cord blood infusion of larger portion through vein using Central Venous Catheter (CVC) on Day 0. Other Name: Cord Blood T Cells Infusion Drug: G-CSF 5 mcg/kg day subcutaneously (may round up to the next vial) beginning on day +1 and continuing till absolute neutrophil count is > 2.5 x 10e^9/L. Other Names: Filgrastim Neupogen Procedure: Ex vivo expanded T cell Infusion Infusion by vein of treated cord blood beginning dose of 1 x 10e^5 T cells/kg on Day 14+.
Experimental: Regimen 2: TBI High Dose Chemotherapy with Total Body Irradiation (TBI)	Radiation: Total Body Irradiation (TBI) 3 Gy of radiation on Days -7,-6, -5 and -4. Drug: Rituximab Regimen 1: 375 mg/m^2 may be given by vein over 4 - 6 hours on Day -9 if needed Regimen 2: 375 mg/m^2 may be given by vein over 4 - 6 hours on Day -8 if needed Other Name: Rituxan Drug: Etoposide 60 mg/m^2 by vein over 1-2 hours as a single dose on Day -3. Other Name: VePesid Drug: Anti-thymocyte globulin (ATG) Regimen 1: 1.25 and 1.75 mg/kg by vein over 4-6 hours on the Days -4 and -3. Regimen 2: 0.5, 1.0 and 1.5 mg/kg by vein over 4-6 hours on respective Days -3, -2, and -1. Other Name: Thymoglublin Drug: Mycophenolate Mofetil (MMF) 15 mg/kg pills twice a day starting on day -3, and continued until Day 100+ after transplant (1 gram may be given by vein if necessary). Other Name: CellCept Drug: Tacrolimus 0.03 mg/kg by vein Day -2 as 24 hour continuous infusion for several weeks. After stem cell transplant, tacrolimus given by mouth 2 times a day for up to 6 months. Other Names: FK506 Prograf Procedure: Cord Blood Infusion Cord blood infusion of larger portion through vein using Central Venous Catheter (CVC) on Day 0. Other Name: Cord Blood T Cells Infusion Drug: G-CSF 5 mcg/kg day subcutaneously (may round up to the next vial) beginning on day +1 and continuing till absolute neutrophil count is > 2.5 x 10e^9/L. Other Names: Filgrastim Neupogen Procedure: Ex vivo expanded T cell Infusion Infusion by vein of treated cord blood beginning dose of 1 x 10e^5 T cells/kg on Day 14+.

Arms

Assigned Interventions

Experimental: Regimen 1: No TBI

High Dose Chemotherapy without Total Body Irradiation (TBI)

Drug: Melphalan

140 mg/m^2 by vein over 30 minutes as a single dose on Day -8

Other Name: Alkeran

Drug: Thiotepa

10 mg/kg by vein over 4 hours as a single dose on Day -7

Drug: Fludarabine

40 mg/m^2 by vein over about 30 minutes 1 time each day on Days -6 through -3.

Other Names:

Fludara
Fludarabine Phosphate

Drug: Rituximab

Regimen 1:

375 mg/m^2 may be given by vein over 4 - 6 hours on Day -9 if needed

Regimen 2:

375 mg/m^2 may be given by vein over 4 - 6 hours on Day -8 if needed

Other Name: Rituxan

Drug: Anti-thymocyte globulin (ATG)

Regimen 1:

1.25 and 1.75 mg/kg by vein over 4-6 hours on the Days -4 and -3.

Regimen 2:

0.5, 1.0 and 1.5 mg/kg by vein over 4-6 hours on respective Days -3, -2, and -1.

Other Name: Thymoglublin

Drug: Mycophenolate Mofetil (MMF)

15 mg/kg pills twice a day starting on day -3, and continued until Day 100+ after transplant (1 gram may be given by vein if necessary).

Other Name: CellCept

Drug: Tacrolimus

0.03 mg/kg by vein Day -2 as 24 hour continuous infusion for several weeks. After stem cell transplant, tacrolimus given by mouth 2 times a day for up to 6 months.

Other Names:

FK506
Prograf

Procedure: Cord Blood Infusion

Cord blood infusion of larger portion through vein using Central Venous Catheter (CVC) on Day 0.

Other Name: Cord Blood T Cells Infusion

Drug: G-CSF

5 mcg/kg day subcutaneously (may round up to the next vial) beginning on day +1 and continuing till absolute neutrophil count is > 2.5 x 10e^9/L.

Other Names:

Filgrastim
Neupogen

Procedure: Ex vivo expanded T cell Infusion

Infusion by vein of treated cord blood beginning dose of 1 x 10e^5 T cells/kg on Day 14+.

Experimental: Regimen 2: TBI

High Dose Chemotherapy with Total Body Irradiation (TBI)

Radiation: Total Body Irradiation (TBI)

3 Gy of radiation on Days -7,-6, -5 and -4.

Drug: Rituximab

Regimen 1:

375 mg/m^2 may be given by vein over 4 - 6 hours on Day -9 if needed

Regimen 2:

375 mg/m^2 may be given by vein over 4 - 6 hours on Day -8 if needed

Other Name: Rituxan

Drug: Etoposide

60 mg/m^2 by vein over 1-2 hours as a single dose on Day -3.

Other Name: VePesid

Drug: Anti-thymocyte globulin (ATG)

Regimen 1:

1.25 and 1.75 mg/kg by vein over 4-6 hours on the Days -4 and -3.

Regimen 2:

0.5, 1.0 and 1.5 mg/kg by vein over 4-6 hours on respective Days -3, -2, and -1.

Other Name: Thymoglublin

Drug: Mycophenolate Mofetil (MMF)

15 mg/kg pills twice a day starting on day -3, and continued until Day 100+ after transplant (1 gram may be given by vein if necessary).

Other Name: CellCept

Drug: Tacrolimus

0.03 mg/kg by vein Day -2 as 24 hour continuous infusion for several weeks. After stem cell transplant, tacrolimus given by mouth 2 times a day for up to 6 months.

Other Names:

FK506
Prograf

Procedure: Cord Blood Infusion

Cord blood infusion of larger portion through vein using Central Venous Catheter (CVC) on Day 0.

Other Name: Cord Blood T Cells Infusion

Drug: G-CSF

5 mcg/kg day subcutaneously (may round up to the next vial) beginning on day +1 and continuing till absolute neutrophil count is > 2.5 x 10e^9/L.

Other Names:

Filgrastim
Neupogen

Procedure: Ex vivo expanded T cell Infusion

Infusion by vein of treated cord blood beginning dose of 1 x 10e^5 T cells/kg on Day 14+.

Show Detailed Description

Eligibility

Ages Eligible for Study:	up to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient must have one of the following hematologic malignancies:
- AML
- ALL
- CML
- NHL
- HD, or
- CLL (Select from Criteria #2 through #7)
Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS; Myelodysplastic syndromes with International Prognostic Scoring System score >2 or myelodysplasia that has not responded to chemotherapy): induction failure, high-risk for relapse 1st remission (with high-risk cytogenetics or FLT3 mutation), 2nd or 3rd complete remission, or 2nd relapse with less than 10% blasts in the bone marrow and/or peripheral blood.
Acute Lymphoblastic Leukemia (ALL): induction failure, 1st complete remission with Philadelphia chromosome or translocation, 2nd or 3rd complete remission, or 2nd relapse with less than 10% blasts in the bone marrow and/or peripheral blood.
Chronic Myelogenous Leukemia (CML) second chronic phase, accelerated phase or blast crisis with less than 10% blasts in the bone marrow and/or peripheral blood and failure of at least one tyrosine kinase inhibitor.
Non-Hodgkin's Lymphoma (NHL): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).
Hodgkin's Disease (HD): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).
Chronic Lymphocytic Leukemia (CLL): Failure of one multi-agent regimen including fludarabine or other nucleoside analog
Patient's Age Criteria: Age >/= 6 months and </= 55 years
Performance score of < 3 (Zubrod score).
Adequate major organ system function as demonstrated by: (SEE CRITERIA #11 through #14)
Left ventricular ejection function of >/= 50%.
Pulmonary function test demonstrating a diffusion capacity of at least 50% predicted. If unable to perform pulmonary function test (most children <6 years of age), pulse oximetry >/= 92% on room air.
Creatinine </= 1.6 mg/dL in adults and </=2 times upper limit of normal in pediatric patients.
SGPT/bilirubin </= 3.0 x normal.
Signed informed consent.
Negative Beta HCG or urine test in females of childbearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization and willing to use an effective contraceptive measure while on the study.
Cord Blood Requirements: Unrelated CB will be used as a source of hematopoietic support if a 5/6 or 6/6 related or 6/6 unrelated bone marrow donor is not available, or if the tempo of the patient's disease dictates it is not in the patient's best interest to wait for an unrelated marrow donor to be procured. The back up cord blood unit must match at 4 of 6 HLA.
An unrelated donor, second cord blood transplant, or autologous stem cells harvested prior to high-dose chemotherapy will be used in the event of graft failure. Based on the health status of the patient, autologous harvest may or may not occur. To be determined by the treating physician. The cord blood unit will be identified prior to enrollment in this study.

Exclusion Criteria:

HIV positive (due to the extreme immunosuppressive nature of allogeneic stem cell transplant)
Patient with active (untreated) CNS disease
Availability of an appropriate, willing, HLA-matched related marrow donor
Active invasive infections.
Pregnant or breast-feeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00972101

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Study Chair:

Laura L. Worth, MD, PHD

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00972101 History of Changes
Other Study ID Numbers:	2006-0075
Study First Received:	September 3, 2009
Last Updated:	October 10, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Blood And Marrow Transplantation
Leukemia
Lymphoma
Pediatrics
Etoposide
Expanded Cord Blood T Cells
Filgrastim
Fludarabine

Melphalan
Mycophenolate Mofetil
Rituximab
Tacrolimus
Thiotepa
Thymoglobulin
Total Body Irradiation

Additional relevant MeSH terms:

Leukemia
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antilymphocyte Serum
Melphalan
Mycophenolate mofetil
Thiotepa
Fludarabine monophosphate
Tacrolimus
Lenograstim

Rituximab
Etoposide
Etoposide phosphate
Fludarabine
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on May 23, 2013