Umbilical Cord Blood Transplant for Hematological Malignancies (UCB)

August 17, 2016 updated by: University of Pennsylvania

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose limiting toxicity (DLT) is defined as grade 4 acute GVHD within the first 90 days following infusion.
Time Frame: 90 Days post Transplant
90 Days post Transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

May 1, 2016

Study Registration Dates

First Submitted

April 29, 2009

First Submitted That Met QC Criteria

April 30, 2009

First Posted (Estimate)

May 1, 2009

Study Record Updates

Last Update Posted (Estimate)

August 19, 2016

Last Update Submitted That Met QC Criteria

August 17, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 02707

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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