Umbilical Cord Blood Transplant for Hematological Malignancies - Full Text View

Sponsored by:	University of Pennsylvania
Information provided by:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00891592

Purpose

This protocol will enroll subjects with advanced hematologic malignancies who do not have a suitable related or unrelated donor to undergo a Stem Cell Transplant.

In this study, subject will undergo a Stem Cell Transplant using Cord Blood. Part of the cord blood will be used for the Stem Cell Transplant and part of the cord blood will be sent to a laboratory in order to grown the T cells (from the cord blood) and increase the activity of the cord blood T cells.

The purpose of this part of the study is to see if it is safe to give study subjects activated T cells made from a small portion of their donor UCB unit immediately after the UCB transplant. Activated T cells have been used safely in stem cell transplantation studies in the past, but they have never been studied UCB transplantation.

Condition	Intervention	Phase
CML AML MDS ALL NHL Multiple Myeloma Hodgkin's Disease	Biological: Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cells Other: Observation Arm	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase 1 Dose Escalation Study of Infusion of ex Vivo cd3/cd28 Costimulated Umbilical Cord Blood-derived t Cells in Adults Undergoing Transplantation for Advanced Hematologic Malignancies

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Hodgkin Disease Multiple Myeloma

U.S. FDA Resources

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

Dose limiting toxicity (DLT) is defined as grade 4 acute GVHD within the first 90 days following infusion. [ Time Frame: 90 Days post Transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	36
Study Start Date:	January 2009
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Dose Escalation Arm: Experimental Subjects with cord blood stored in more than one fraction will be enrolled into Dose Escalation Arm. Subjects will receive Cord Blood Stem Cell Transplant followed by expanded Cord Blood T cells on Day 0.	Biological: Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cells Single infusion of Cord Blood Cells AND Single Infusion of ex vivo CD3/CD28 costimulated Umbilical Cord Blood T cells. Table 6: Dose escalation (Dose level CD3+ cell dose) 1xE5 cells/kg 2xE6 cells/kg 3xE7 cells/kg 4xE8 cells/kg
Observation Arm: Active Comparator Subjects with cord blood stored in one fraction will be enrolled into the Observation Arm. Subjects will receive Cord Blood Stem Cell Transplant on Day 0.	Other: Observation Arm Single infusion of Cord Blood Cells

Detailed Description:

The main study intervention includes CD3/CD28 ex vivo costimulated T cells derived from a thawed umbilical cord blood unit, co-infused following a myeloablative conditioning regimen.

Activated T cells are T cells that have been activated in the laboratory by exposure to 2 compounds or molecules called CD3 and CD28; when T cells are exposed to both of these compounds at the same time, they become activated or "stimulated" and may be more effective in fighting infections, cancer cells, and promoting the recovery of red cells, white cells, and platelets after transplantation. At the Hospital of the University of Pennsylvania, activated T cells are prepared at the Clinical Cell and Vaccine Production Facility, also known as the CVPF.

Eligibility

Ages Eligible for Study:	21 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria.

Relapsed or persistent advanced hematologic malignancy; incurable with standard chemotherapy and eligible for allogeneic HSCT, including:
CHRONIC MYELOGENOUS LEUKEMIA (CML). Subjects in accelerated or blast phase or subjects in chronic phase with inadequate response to Imatinib or intolerant to Imatinib.
ACUTE MYELOGENOUS LEUKEMIA (AML). Subject with high risk disease in first complete remission (CR). High risk disease includes the following cytogenetic abnormalities: monosomy 7, deletion 5, trisomy 8, inversion 3, t(3;3), t(6;9), or t(6;11). Subjects with complex cytogenetic abnormalities (more than 3 chromosomal abnormalities).
ACUTE MYELOGENOUS LEUKEMIA (AML). Subjects with diagnosis of AML after receiving chemotherapy, radiation therapy or biospy showing myelodysplastic syndrome.
ACUTE MYELOGENOUS LEUKEMIA (AML). Subjects with persistent AML after 2 cycles of standard induction chemotherapy.
ACUTE MYELOGENOUS LEUKEMIA (AML). Subjects in first complete remission.
MYELODYSPLASTIC SYNDROME (MDS). Subjects with intermediate or high risk disease based upon International Prognostic Scoring System.
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL). Subjects with Philadelphis Chromosome (have t(9;22) cytogenetic abnormality) or molecular documentation for BCR-ABL translocation.
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL). Subjects with primary refractory disease or subjects in 1st complete remission.
NHL or HODKIN'S DISEASE. Subjects who relapse following autologus Stem Cell Transplant.
IDOLENT NHL. Subjects with progressive disease following > 2 regimens.
MULTIPLE MYELOMA. Subjects who relapse following following autologus Stem Cell Transplant.
Adults age 21-50.
Expected survival . 4 weeks.
Subjects with no suitable related or unrelated donor for Stem Cell Transplant.
Subject has suitable Umbilical Cord Blood (UCB) unit available.
Subject has: Ejection fraction > 45%; DLCO.45% predicted; Creatinine < 2; Total bilirubin < 2X normal; Transaminases < 2X normal.
Subject is capable of giving informed consent.

Exclusion Criteria:

Subject is pregnant or lactating.
Subject has an uncontrolled infection.
Subject has an active or untreated disease involving the central nervous system.
Subject has an active or uncontrolled medical condition that would preclude participation in the protocol.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00891592

Contacts

Contact: Chris Nowacyzk, BS	215-746-8903	cnow@mail.med.upenn.edu
Contact: Lester Lledo, MSN, CRNP	215-746-6040	lledol@mail.med.upenn.edu

Locations

United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

University of Pennsylvania

Investigators

Principal Investigator:	David Porter, MD	University of Pennsylvania
Principal Investigator:	Elizabeth Hexner, MD	University of Pennsylvania

More Information

Additional Information:

Abramson Cancer Center Clinical Trials This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Pennsylvania ( Carl H. June, MD ; Director, Translational Research Programs, Abramson Cancer Center, Professor of Pathology and Laboratory Medicine )
Study ID Numbers:	UPCC 02707
Study First Received:	April 29, 2009
Last Updated:	August 6, 2009
ClinicalTrials.gov Identifier:	NCT00891592 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:

AML
MDS
ALL

NHL
Multiple Myeloma
Hodgkin's

Study placed in the following topic categories:

Immunoproliferative Disorders
Hodgkin Lymphoma, Adult
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Vascular Diseases
Hodgkin's Disease
Paraproteinemias

Hemostatic Disorders
Multiple Myeloma
Lymphatic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Hodgkin Disease
Lymphoma
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Blood Protein Disorders
Vascular Diseases
Paraproteinemias
Hemostatic Disorders
Multiple Myeloma

Lymphatic Diseases
Neoplasms
Hemorrhagic Disorders
Cardiovascular Diseases
Lymphoproliferative Disorders
Hodgkin Disease
Lymphoma
Neoplasms, Plasma Cell

ClinicalTrials.gov processed this record on September 02, 2009