Activated White Blood Cells in Treating Patients Undergoing an Autologous Stem Cell Transplant for Newly Diagnosed Stage II or Stage III Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00566098
First received: November 30, 2007
Last updated: April 16, 2013
Last verified: April 2013
  Purpose

RATIONALE: Activating white blood cells in the laboratory may help them kill more cancer cells when they are put back in the body. This may be an effective treatment for patients undergoing a stem cell transplant for multiple myeloma.

PURPOSE: This phase I/II trial is studying the side effects of activated white blood cells and to see how well they work in treating patients who are undergoing a stem cell transplant for newly diagnosed stage II or stage III multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: therapeutic autologous lymphocytes
Biological: therapeutic tumor infiltrating lymphocytes
Drug: melphalan
Procedure: autologous hematopoietic stem cell transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]
  • Hematopoietic engraftment [ Designated as safety issue: No ]
  • Response rates utilizing the Blade criteria, including complete response (CR) rate, near complete response (nCR) rate, very good partial response (VGPR) rate, partial response (PR) rate, minimal response (MR) rate, overall response rate (CR, VGPR, ... [ Designated as safety issue: No ]
  • Generation of activated marrow infiltrating lymphocytes (aMILs) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • T-cell reconstitution, including absolute lymphocyte counts, CD3+/ CD4+/ CD8+ T-cell counts [ Designated as safety issue: No ]
  • Progression-free survival and overall survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • Pneumococcal-specific vaccine responses [ Designated as safety issue: No ]
  • Anti-tumor immune responses [ Designated as safety issue: No ]
  • Delayed-type hypersensitivity (DTH) responses [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: November 2007
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the safety and response rate of activated marrow infiltrating lymphocytes (aMILs) in patients undergoing autologous peripheral blood stem cell transplantation for newly diagnosed, stage II-III multiple myeloma.
  • Determine the overall in vitro fold-expansion and assess pre- and post-expansion for myeloma T-cell specificity in assessing the feasibility of generating aMILs from myeloma patients.
  • Assess the toxicity of aMILs.
  • Evaluate the effect of aMILs on hematopoietic engraftment, including neutrophil engraftment, platelet engraftment, and primary graft failure (if failure occurs).
  • Evaluate response rates utilizing the Blade criteria, including the complete response (CR) rate, near complete response (nCR) rate, very good partial response (VGPR) rate, partial response (PR) rate, minimal response (MR) rate, and overall response rate (CR, VGPR, PR, MR).

Secondary

  • Evaluate T-cell reconstitution, including absolute lymphocyte counts, CD3+, CD4+, and CD8+ T-cell counts.
  • Evaluate progression-free survival and overall survival.
  • Evaluate anti-tumor immune response.
  • Determine pneumococcal-specific vaccine responses.
  • Determine delayed-type hypersensitivity (DTH) responses.

OUTLINE: Patients undergo collection of marrow infiltrating lymphocytes (MILs)* either at diagnosis prior to the initiation of induction therapy or upon completion of induction therapy. The MILs bone marrow product undergo ex vivo activation and expansion of T cells for 7-8 days to produce activated marrow infiltrating lymphocytes (aMILs). Patients then undergo stem cell mobilization and leukapheresis to collect the peripheral blood stem cells 12 days after mobilization. Patients receive melphalan IV over 20-30 minutes on days -2 and -1 and undergo a peripheral blood stem cell transplantation on day 0 as planned. Patients receive aMILs infusion on day 3. Patients receive pneumococcal polyvalent vaccine on day 21.

NOTE: *Patients who have completed induction therapy receive pneumococcal polyvalent vaccine approximately 2 weeks prior to MILs collection; patients undergoing MILs collection prior to starting induction therapy do not receive a pre-transplantation vaccine.

Blood and bone marrow samples are collected periodically for laboratory correlative studies.

After completion of study treatment, patients are followed periodically for up to 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma

    • Newly diagnosed disease
    • Durie-Salmon stage II or III disease
  • Measurable disease, defined by any of the following:

    • Measurable serum and/or urine M-protein levels documented and available prior to induction therapy
    • Positive serum free light chain assay
  • Must have completed a minimum of 3 courses of myeloma specific therapy
  • Candidate for autologous stem cell transplantation
  • Patients who have achieved a complete remission at the time of bone marrow harvest for marrow infiltrating lymphocytes (MILs) expansion are not eligible
  • No evidence of spinal cord compression
  • Diagnosis of the following cancers are not allowed:

    • POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
    • Non-secretory myeloma (no measurable protein on serum free light chain assay)
    • Plasma cell leukemia
  • No amyloidosis

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 6 months
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and up to day 180
  • Corrected serum calcium < 11 mg/dL and no evidence of symptomatic hypercalcemia
  • Total bilirubin ≤ 2.0 times upper limit of normal (ULN)
  • ALT ≤ 2.0 times ULN
  • Serum creatinine < 2.0 mg/dL
  • No history of other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer
  • No history of autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus) requiring systemic treatment

    • Hypothyroidism without evidence of Graves' disease or Hashimoto thyroiditis is allowed
  • No infection requiring treatment with antibiotics, antifungal, or antiviral agents within the past 7 days
  • No HIV infection
  • No major organ system dysfunction including, but not limited to, the following:

    • New York Heart Association class III or IV congestive heart failure
    • Pulmonary disease requiring the use of inhaled steroids or bronchodilators
    • Renal, hepatic, gastrointestinal, neurologic, or psychiatric dysfunction that would impair ability to participate in the study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior hematopoietic stem cell transplantation
  • At least 3 weeks since prior corticosteroids (i.e., glucocorticoids)
  • At least 3 weeks since prior myeloma-specific therapy
  • At least 4 weeks since participation in any clinical trial that involved an investigational drug or device
  • No concurrent therapy with any of the following:

    • Corticosteroids (e.g., hydrocortisone, prednisone, prednisolone, dexamethasone [Decadron])

      • Inhaled steroids used for treatment of allergic rhinitis or pulmonary disease allowed
    • Thalidomide
    • Interferon
    • Growth factors, interleukins, or other cytokines (except filgrastim [G-CSF] as outlined in the protocol, or erythropoietin)
    • Cytotoxic chemotherapy agents (except cyclophosphamide for stem cell mobilization and high-dose melphalan)
    • Immunosuppressive drugs
    • Experimental therapies
    • Radiotherapy
  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: NCT00566098

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Ivan Borrello, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00566098     History of Changes
Other Study ID Numbers: J0770 JHU, P30CA006973, JHOC-J0770
Study First Received: November 30, 2007
Last Updated: April 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 19, 2014