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Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma

Phase 1/Phase 2
18 Years
Open (Enrolling)
Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma



- 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,


- 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.

Inclusion Criteria


- 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


- 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

- 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


- 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

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

Ivan Borrello, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:

J0770 JHU



Start Date:

November 2007

Completion Date:

December 2013

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410