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Th1/Tc1 Immunotherapy Following Stem Cell Transplantation in Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by National Institutes of Health Clinical Center (CC)
Hackensack University Medical Center
Georgetown University
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) Identifier:
First received: November 10, 2010
Last updated: October 20, 2016
Last verified: September 2016


- 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.

Condition Intervention Phase
Multiple Myeloma
Procedure: Adoptive Immunotherapy
Biological: Rapamycin-Generated Autologous Th1/Tc1 Cells
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Evaluate feasibility and toxicity [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Death ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Time of progression ] [ Designated as safety issue: No ]

Estimated Enrollment: 86
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)
Arms Assigned Interventions
Experimental: 1
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.

Detailed Description:


  • 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.

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


Criteria for Cohort A (recently diagnosed subjects; to receive 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 (IgG or 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 MM, as defined by: serum M-protein greater than or euqal 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):

  • Age greater than or equal to 18 years and less than or equal to 75 years. In subjects between 65 and 75 years of age, physiologic age and co-morbidity will be thoroughly evaluated before enrolling. Specifically, any history of cardio-vascular pathology or symptoms, not clearly fitting the exclusion criteria will prompt an evaluation by a Clinical Center Cardiologist and eligibility will be considered on a case-by-case basis.
  • For Cohort A only, high-dose chemotherapy and AHCT must be planned; with amendment K, post-transplant maintenance therapy will not be permitted.
  • Karnofsky performance status 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 MUGA or 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,
  • AST and 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 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 NYHY, 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.
  • HIV seropositive
  • Patients known or found to be pregnant.
  • Patients of childbearing age who are unwilling to practice contraception.

Patients may be excluded at the discretion of the PI if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01239368

Contact: Daniel H Fowler, M.D. (240) 760-6164

United States, District of Columbia
Georgetown University Recruiting
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
Sponsors and Collaborators
National Cancer Institute (NCI)
Hackensack University Medical Center
Georgetown University
Principal Investigator: Daniel H Fowler, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Responsible Party: National Cancer Institute (NCI) Identifier: NCT01239368     History of Changes
Other Study ID Numbers: 110016  11-C-0016 
Study First Received: November 10, 2010
Last Updated: October 20, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Multiple Myeloma
High Risk
Newly Diagnosed
Adoptive Immunotherapy

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on December 08, 2016