Activated White Blood Cells With ASCT for Newly Diagnosed Multiple Myeloma

NCT ID: NCT00566098

Last Updated: 2023-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2018-10-31

Brief Summary

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.

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ASCT+MILs

Autologous stem cell transplant with a conditioning regimen of melphalan 100 mg/m\^2 on each of Days -2 and -1. Infusion of activated marrow infiltrating lymphocytes (MILs) on Day 3. PCV13 vaccine will be given before and/or after Day 0 depending on when participants are enrolled.

Group Type: EXPERIMENTAL

MILs

Intervention Type: BIOLOGICAL

Melphalan

Intervention Type: DRUG

PCV13

Intervention Type: BIOLOGICAL

Interventions

MILs

Intervention Type: BIOLOGICAL

Melphalan

Intervention Type: DRUG

PCV13

Intervention Type: BIOLOGICAL

Other Intervention Names

Marrow infiltrating lymphocytes; Activated marrow infiltrating lymphocytes; aMILs; Alkeran; Prevnar

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ivan Borrello, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

Noonan KA, Huff CA, Davis J, Lemas MV, Fiorino S, Bitzan J, Ferguson A, Emerling A, Luznik L, Matsui W, Powell J, Fuchs E, Rosner GL, Epstein C, Rudraraju L, Ambinder RF, Jones RJ, Pardoll D, Borrello I. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med. 2015 May 20;7(288):288ra78. doi: 10.1126/scitranslmed.aaa7014.

Reference Type: RESULT

PMID: 25995224 (View on PubMed)

Other Identifiers

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00012038

Identifier Type: OTHER

Identifier Source: secondary_id

J0770

Identifier Type: -

Identifier Source: org_study_id