Th1/Tc1 Immunotherapy Following Stem Cell Transplantation in Multiple Myeloma
NCT ID: NCT01239368
Last Updated: 2019-12-10
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE1/PHASE2
34 participants
INTERVENTIONAL
2010-11-10
2017-08-16
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
\- 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.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
* 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Cohort B - Relapsed Multiple Myeloma
Th1 (type 1 T helper cells)/Tc1 (T cytotoxic cells, type 1) .Rapamycin (Rapa) for Relapsed Multiple Myeloma
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).
Th1/Tc1 Rapa Cell Therapy
Th1/Tc1Rapa: 5 x 10e(6) cells/kg
Cohort A - Prevention of Relapse
Th1/Tc1.Rapa Prevention of Relapse
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).
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.
Th1/Tc1 Rapa Cell Therapy
Th1/Tc1Rapa: 5 x 10e(6) cells/kg
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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).
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.
Th1/Tc1 Rapa Cell Therapy
Th1/Tc1Rapa: 5 x 10e(6) cells/kg
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Criteria for Cohort A (recently diagnosed subjects; to receive autologous hematopoietic cell transplantation (AHCT)):
* Must have presence of clonal plasma cells in the bone marrow greater or equal to 10% or biopsy proven plasmacytoma
* Must have either:
1. presence of an M-component (Immunoglobulin G (IgG) or Immunoglobulin G (IgA)) in serum greater or equal to 1g/dl or in urine greater or equal to 200 mg/24 h; or
2. presence of an abnormal serum free light chain (FLC) ratio on the serum FLC assay.
Criteria for Cohort B (multiply relapsed multiple myeloma):
* Must have measurable multiple myeloma (MM), as defined by: serum M-protein greater than or equal to 1 g/dL, urine M-protein greater than or equal to 200 mg/24 hours, involved serum free light chain (FLC) level greater than or equal to 10 mg/dL, biopsy proven plasmacytoma, or more than 30% bone marrow plasma cells.
* Must have received at least 2 different treatment regimens for MM.
Other eligibility criteria (applies to both Cohort A and Cohort B, unless specified):
Exclusion Criteria
* Karnofsky performance status (KPS) of 70% or greater. Lower KPS down to 50% may be acceptable if the restriction of activity is solely due to intractable pain from myeloma lesions.
* Ejection fraction (EF) by multi-gated acquisition scan (MUGA) or two-dimensional (2-D) echocardiogram within institution normal limits. In case of low EF, the subject may remain eligible after a stress echocardiogram is performed if the EF is more than 35% and if the increase in EF with stress is estimated at 10% or more.
* Serum creatinine less than or equal to 2.5 mg/dl,
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 times the upper limit of normal.
* Bilirubin less than or equal to1.5 (except if due to Gilbert's disease).
* Corrected carbon monoxide diffusing capacity (DLCO) greater than or equal to 50% on Pulmonary Function Tests
* No history of abnormal bleeding tendency or predisposition to repeated infections.
* Patients must be able to give informed consent
* Prior allogeneic stem cell transplantation
* Hypertension not adequately controlled by 3 or less medications.
* History of cerebro-vascular accident within 6 months of enrollment.
* History of documented pulmonary embolus within 6 months of enrollment.
* Clinically significant cardiac pathology: myocardial infarction within 6 months prior to enrollment, Class III or IV heart failure according to New York Heart Association (NYHA), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
* Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.
* Human immunodeficiency virus (HIV) seropositive
* Patients known or found to be pregnant or who is unwilling to stop breast-feeding.
* Patients of childbearing age who are unwilling to practice contraception or other means of avoiding pregnancy.
Patients may be excluded at the discretion of the principal investigator (PI) if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.
18 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Hackensack Meridian Health
OTHER
Georgetown University
OTHER
National Cancer Institute (NCI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Steven Pavletic, M.D.
Principal Investigator
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Steven Z Pavletic, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
National Institutes of Health (NIH) Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.
Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990 Feb;33(2):86-9. doi: 10.1002/ajh.2830330203.
Tosi P, Zamagni E, Cellini C, Plasmati R, Cangini D, Tacchetti P, Perrone G, Pastorelli F, Tura S, Baccarani M, Cavo M. Neurological toxicity of long-term (>1 yr) thalidomide therapy in patients with multiple myeloma. Eur J Haematol. 2005 Mar;74(3):212-6. doi: 10.1111/j.1600-0609.2004.00382.x.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Related Links
Access external resources that provide additional context or updates about the study.
NIH Clinical Center Detailed Web Page
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
11-C-0016
Identifier Type: -
Identifier Source: secondary_id
110016
Identifier Type: -
Identifier Source: org_study_id