Th1/Tc1 Immunotherapy Following Stem Cell Transplantation in Multiple Myeloma

Summary

Background:

\- Cancer development is associated with problems in immune system functions, which prevent the body from attacking and destroying the abnormal cells that lead to tumor growth. Research has suggested that certain white blood cells, known as Th1 (type 1 T helper cells) and Th2 T cells (type 2 T helper cells), are affected in individuals with some kinds of cancer -- when the proportion of Th2 cells is greater than Th1 cells, the immune systems ability to fight off the growth of malignant tumors is weakened. Researchers are interested in determining if an infusion of specially modified Th1 cells, in addition to stem cell transplant, is a safe and effective treatment for individuals with forms of multiple myeloma that might not respond well to standard treatments alone.

Objectives:

\- To determine the safety and effectiveness of the infusion of modified Th1 white blood cells, in conjunction with standard treatment, as a treatment for individuals who have been diagnosed with high-risk forms of multiple myeloma.

Eligibility:

* Individuals age 18 to 75 who have been newly diagnosed with high-risk multiple myeloma and who have received no or minimal treatment (Cohort A).
* Individuals age 18 to 75 who have relapsed multiple myeloma, as defined by measurable disease after at least 2 prior treatment regimens.

Design:

* Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies. Some participants may also have a bone marrow or other type biopsy to evaluate the state of their disease.
* White blood cells will be collected from the participants through an apheresis procedure, which will collect and separate the white blood cells and return the rest of the blood to the participant.
* The collected cells will be grown and expanded under special conditions in the laboratory and stored frozen until participants receive standard of care treatment for multiple myeloma, including a stem cell transplant.
* Participants will receive an infusion of the modified Th1 cells a few weeks after the transplant, and will remain in the hospital for a few days after receiving the cells to monitor the possible immediate effects of the treatment.
* Participants will have regular follow-up visits to study the long-term effects of the modified Th1 cell infusion.

Conditions

• Myeloma, Plasma-Cell
• Myeloma-Multiple
• Myelomatosis

Interventions

PROCEDURE

Adoptive Immunotherapy

Th1 (type 1 T helper cells)/Tc1 (T cytotoxic cells, type 1) Rapa cell infusion will be evaluated after administration of a 7-day or 14-day course of immune depleting chemotherapy (pentostatin plus cyclophosphamide regimen).

BIOLOGICAL

Rapamycin-Generated Autologous Th1/Tc1 Cells (modified primary human T cells)

Six Th1/Tc1 Rapa cell doses will be tested in cohorts of 1-6 subjects each: ranging from 10e(5) to 15 x 10e(6) cells/kg of body weight.

BIOLOGICAL

Th1/Tc1 Rapa Cell Therapy

Th1/Tc1Rapa: 5 x 10e(6) cells/kg

Sponsors & Collaborators

• Hackensack Meridian Health

  collaborator OTHER

• Georgetown University

  collaborator OTHER

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven Z Pavletic, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-11-10

Primary Completion

2017-08-16

Completion

2017-08-16

FDA Drug

Yes

Countries

• United States

Study Locations