Myeloma, Plasma-Cell Clinical Trial
Official title:
Rapamycin-Resistant T Cell Therapy of Multiple Myeloma: Relapse Prevention and Relapse Therapy
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.
Background:
- 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 (type 1 T
helper cells)/Tc1 (T cytotoxic cells, type 1) polarized T cells (Th1/Tc1.Rapamycin
(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.
Objectives:
Primary
Dose escalation study
Evaluate the feasibility and toxicity of an infusion of autologous, ex vivo
rapamycin-generated, anti-cluster of differentiation 3 (CD3) and anti-cluster of
differentiation 28 (CD28) co-stimulated, Th1/Tc1 lymphocytes (Th1/Tc1.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 partial response (PR)/complete response (CR)
rate of Th1/Tc1.Rapa cell therapy.
Eligibility:
- For Cohort A 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.
Design:
- 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.
;
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