Activated White Blood Cells With ASCT for Newly Diagnosed Multiple Myeloma

NCT00566098 | Completed Phase 1 Results

• 3 other identifiers: J0770P30CA006973NA_00012038
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (3)

• Hematopoietic Engraftment

  Days to absolute neutrophil count \> 500 cells per microliter.

  Up to 1 year

• Disease Response

  Percentage of participants with partial or complete response by Bladé criteria. Partial response is defined as a \>= 50% decrease in serum paraprotein or 90% decrease in urinary light chains (for participants without measurable serum paraprotein). Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells.

  Up to 2 years

• Feasibility of MILs Generation as Assessed by Percentage of Participants With Successful MIL Generation

  Success rate of expanding MILs in vitro and obtaining a protocol-specified product.

  Up to 1 year

Secondary Outcomes (4)

• T-cell Reconstitution as Determined by Absolute Lymphocyte Count (ALC)

  Days 14, 28, 60, 180, and 360

• Survival

  Up to 129 months

• Pneumococcal-specific Vaccine Responses

  At time of bone marrow harvest, Day 60 post-transplant, Day 180 post-transplant, and Day 360 post-transplant

• Anti-tumor Immune Responses

  At time of bone marrow harvest, Day 60 post-transplant, Day 180 post-transplant, and Day 360 post-transplant

Study Arms (1)

ASCT+MILs

EXPERIMENTAL

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.

Biological: MILs; Drug: Melphalan; Biological: PCV13

Interventions

MILs BIOLOGICAL

Also known as: Marrow infiltrating lymphocytes, Activated marrow infiltrating lymphocytes, aMILs

ASCT+MILs

Melphalan DRUG

Also known as: Alkeran

ASCT+MILs

PCV13 BIOLOGICAL

Also known as: Prevnar

ASCT+MILs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Related Publications (1)

• 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.

  PMID: 25995224 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

N(1)-methyl-2-lysergic acid diethylamide; Melphalan; Heptavalent Pneumococcal Conjugate Vaccine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pneumococcal Vaccines; Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Vaccines, Combined

Results Point of Contact

• Title: Ivan Borrello, MD
• Organization: Johns Hopkins University

iborrell@jhmi.edu

4109554967

Study Officials

• Ivan Borrello, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2007
• First Posted: December 3, 2007
• Study Start: November 1, 2007
• Primary Completion: June 1, 2014
• Study Completion: October 1, 2018
• Last Updated: May 26, 2023
• Results First Posted: December 19, 2018

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)