Th1/Tc1 Immunotherapy Following Stem Cell Transplantation in Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Hackensack University Medical Center
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01239368
First received: November 10, 2010
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

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 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.

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 (4 months or less) yet..

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 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
Drug: Th1/Tc1 product
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-Center Phase I Study of Th1/Tc1 Immunotheraphy Following Autologous Hematopoietic Progenitor Cell Transplantation in High Risk Multiple Myeloma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 newly diagnosed with high-risk multiple myeloma. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall Survival [ Designated as safety issue: No ]
  • Disease-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 41
Study Start Date: October 2010
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Procedure: Adoptive Immunotherapy
N/A
Drug: Th1/Tc1 product
N/A

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

MULTIPLE MYELOMA CRITERIA:

Criteria for newly or recently diagnosed subjects

  • Must have presence of clonal plasma cells in the bone marrow greater or equal to 10% or a documented clonal plasmacytoma
  • Must have either:

    1. 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.
  • Must have one of the following:

    1. Calcium elevation greater than 11.5 mg/dl (2.65 mmol/l)
    2. Renal insufficiency: serum creatinine greater than 2 mg/dl (177 mmol/l)
    3. Hemoglobin less than 10g/dl (12.5 mmol/l) or 2 g/dl (1.25 mmol/l) below lower normal
    4. Bone disease (lytic lesions or osteopenia)
    5. Other evidence of disease activity: repeated infections, secondary amyloidosis, hyperviscosity, hypogammablobulinemia
  • Must have high risk disease defined as the presence of any of the following:

    • Stage II and III of the International Staging System defined as follows:

      • stage I: - serum (Beta)2-microglobulin less than 3.5 mg/l plus

        -----serum albumin greater or equal to 3.5 g/dl

      • stage II: neither stage I nor III
      • stage III: serum (Beta)2-microglobulin greater or equal to 5.5 mg/L

        • del 13 or aneuploidy (by metaphase analysis33)
        • del 17p13 by FISH or mutated p53
        • (4;14) by FISH31
        • (14;16) or t(14;20) by FISH
        • plasmablastic morphology at diagnosis(35)
        • circulating myeloma cells by FACS (CD38+/CD45low) post induction therapy(36)
        • High-risk disease as defined in a 70-gene ( MyPRS (TM)) or the 17-gene condensed microarrays

OTHER ELIGIBILITY CRITERIA:

  • 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 wil be considered on a case-by-case basis
  • Must have received no more than 6 cycles of induction therapy for Multiple Myeloma.
  • The planned High-Dose chemotherapy must consist of melphalan only and may be followed by a post-ASCT consolidation.
  • Karnofsky performance status of 70% or greater (ECOG 0 or 1). Lower KPS down to 50% or ECOG of 2 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

DECISION TO ENROLL ON COHORT 5 B

The decision to enroll on cohort 5B or on cohort 6 will be made as follows:

  • A subject will be enrolled on the cohort that has the smallest number of accrued subjects of these two cohorts.
  • In case of a tie, the subject will be enrolled on the cohort that did not enroll the previous subject.

EXCLUSION CRITERIA:

  • 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 ClinicalTrials.gov identifier: NCT01239368

Contacts
Contact: Daniel H Fowler, M.D. (301) 402-8641 dhfowler@helix.nih.gov

Locations
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
Hackensack University Medical Center
Investigators
Principal Investigator: Daniel H Fowler, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01239368     History of Changes
Other Study ID Numbers: 110016, 11-C-0016
Study First Received: November 10, 2010
Last Updated: March 25, 2014
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on October 16, 2014