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Umbilical Cord Blood Transplant for Hematological Malignancies (UCB)

Primary Purpose

CML, AML, MDS

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cells
Observation Arm
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for CML focused on measuring AML, MDS, ALL, NHL, Multiple Myeloma, Hodgkin's

Eligibility Criteria

21 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dose Escalation Arm

Observation Arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Dose limiting toxicity (DLT) is defined as grade 4 acute GVHD within the first 90 days following infusion.

Secondary Outcome Measures

Full Information

First Posted
April 29, 2009
Last Updated
August 17, 2016
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT00891592
Brief Title
Umbilical Cord Blood Transplant for Hematological Malignancies
Acronym
UCB
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CML, AML, MDS, ALL, NHL, Multiple Myeloma, Hodgkin's Disease
Keywords
AML, MDS, ALL, NHL, Multiple Myeloma, Hodgkin's

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Observation Arm
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cells
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Observation Arm
Intervention Description
Single infusion of Cord Blood Cells
Primary Outcome Measure Information:
Title
Dose limiting toxicity (DLT) is defined as grade 4 acute GVHD within the first 90 days following infusion.
Time Frame
90 Days post Transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Porter, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elizabeth Hexner, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26858124
Citation
Hexner EO, Luger SM, Reshef R, Jeschke GR, Mangan JK, Frey NV, Frank DM, Richman LP, Vonderheide RH, Aqui NA, Rosenbach M, Zhang Y, Chew A, Loren AW, Stadtmauer EA, Levine BL, June CH, Emerson SG, Porter DL. Infusion of CD3/CD28 costimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment. Am J Hematol. 2016 May;91(5):453-60. doi: 10.1002/ajh.24303. Epub 2016 Apr 4.
Results Reference
derived
Links:
URL
http://www.penncancer.org/clinicaltrials.cfm
Description
Abramson Cancer Center Clinical Trials

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Umbilical Cord Blood Transplant for Hematological Malignancies

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