Umbilical Cord Blood Transplant for Hematological Malignancies (UCB)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00891592
First received: April 29, 2009
Last updated: January 31, 2013
Last verified: January 2013
  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, subjects 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 grow 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 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: 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:


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 2013
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation Arm
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
Active Comparator: Observation Arm
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 biopsy 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 Philadelphia 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 autologous Stem Cell Transplant.
  • INDOLENT NHL. Subjects with progressive disease following > 2 regimens.
  • MULTIPLE MYELOMA. Subjects who relapse following following autologous 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
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: NCT00891592

Locations
United States, Pennsylvania
University of Pennsylvania
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:
No publications provided

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00891592     History of Changes
Other Study ID Numbers: UPCC 02707
Study First Received: April 29, 2009
Last Updated: January 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
AML
MDS
ALL
NHL
Multiple Myeloma
Hodgkin's

Additional relevant MeSH terms:
Hodgkin Disease
Multiple Myeloma
Neoplasms, Plasma Cell
Hematologic Neoplasms
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Neoplasms by Site

ClinicalTrials.gov processed this record on August 19, 2014