Umbilical Cord Blood Transplant for Hematological Malignancies

Multiple Myeloma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00891592
• Other study ID #: UPCC 02707
• Status: Completed
• Phase: Phase 1
• First received: April 29, 2009
• Last updated: August 17, 2016
• Start date: January 2009
• Est. completion date: May 2016

Study information

• Verified date: August 2016
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: May 2016
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 50 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• ALL
• AML
• CML
• Hodgkin Disease
• Hodgkin's Disease
• MDS
• Multiple Myeloma
• Neoplasms, Plasma Cell
• NHL

Intervention

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

Other:
• Observation Arm
Single infusion of Cord Blood Cells

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity (DLT) is defined as grade 4 acute GVHD within the first 90 days following infusion.		90 Days post Transplant	Yes

External Links

•   Abramson Cancer Center Clinical Trials