Th1/Tc1 Immunotherapy Following Stem Cell Transplantation in Multiple Myeloma
- 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 and Th2 T cells, are affected in individuals with some kinds of cancer -- when the proportion of Th2 cells is greater than Th1 cells, the immune system s 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.
- 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.
- Individuals age 18 to 75 who have been newly diagnosed with high-risk multiple myeloma and who have received no or minimal treatment (4 months or less) yet..
- 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 all the 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.
Procedure: Adoptive Immunotherapy
Biological: Rapamycin-Generated Autologous Th1/Tc1 Cells
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Rapamycin-Resistant T Cell Therapy of Multiple Myeloma: Relapse Prevention and Relapse Therapy|
- Evaluate feasibility and toxicity [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- Overall Survival [ Time Frame: Death ] [ Designated as safety issue: No ]
- Disease-free survival [ Time Frame: Time of progression ] [ Designated as safety issue: No ]
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||August 2019|
|Estimated Primary Completion Date:||November 2018 (Final data collection date for primary outcome measure)|
Adoptive Immunotherapy +Rapamycin-Generated Autologous Th1/Tc1 Cells
Procedure: Adoptive Immunotherapy
Th1.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
Six Th1.rapa cell doses will be tested in cohorts of 1-6 subjects each: ranging from 10e5 to 15 x 10e6 cells/kg of body weight.
- Autologous Hematopoietic Cell Transplantation (AHCT), which represents the standard of care for newly diagnosed Multiple Myeloma (MM), is not curative therapy. New approaches to prevent relapse after AHCT and to treat relapse are needed.
- In murine models, we used ex vivo culture to generate rapamycin-resistant, Th1/Tc1 polarized T cells (Th1/Tc1.Rapa cells) that were both rapamycin-resistant and apoptosis-resistant with an increased in vivo survival and in vivo function.
- Because Th1 /Tc1 polarized lymphocytes are pivotal in anti-tumor effects, we hypothesize that adoptive transfer of Th1/Tc1Rapa cells will be of benefit to MM patients.
Dose escalation study
Evaluate the feasibility and toxicity of an infusion of autologous, ex vivo rapamycin-generated, anti-CD3 and anti-CD28 co-stimulated, Th1/Tc1 lymphocytes (Th1.rapa cells) in subjects diagnosed with high-risk multiple myeloma following AHCT.
MM Relapse Prevention and Treatment Cohorts
- For Cohort A, in newly diagnosed MM patients who have received AHCT, evaluate the safety of a defined regimen of Th1/Tc1.Rapa cell therapy and determine progression-free survival.
- For Cohort B, in relapsed MM, determine the PR/CR rate of Th1/Tc1.Rapa cell therapy.
- For CohortA relapse prevention, patients with MM (normal- or high-risk) who are receiving induction therapy and subsequent AHCT.
- For Cohort B relapse therapy, patients with MM who have measurable disease after at least 2 prior treatment regimens.
- For Cohort A, patients will receive two infusions of autologous Th1/Tc1.Rapa cells (at one and two months post-AHCT; each infusion preceded by a 7-day course of immune modulating chemotherapy [pentostatin plus low-dose cyclophosphamide; PC regimen].
- For Cohort B relapse therapy, patients will up to four infusions of Th1/Tc1.Rapa cells, with each infusion preceded by either a 7-day or 14-day PC regimen.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01239368
|Contact: Daniel H Fowler, M.D.||(240) firstname.lastname@example.org|
|United States, District of Columbia|
|Washington, District of Columbia, United States, 20007-2197|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|United States, New Jersey|
|Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States|
|Principal Investigator:||Daniel H Fowler, M.D.||National Cancer Institute (NCI)|