Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic Granulocyte Macrophage Colony-stimulating Factor (GM-CSF)-Based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma

NCT01045460 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: J0997NA_00029491
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Patient Population: Patients with active myeloma (Stage II/III) that have completed induction therapy and are eligible for an autologous stem cell transplant. Number of Patients: Will treat a total of 32 evaluable patients in a 1:1 randomization of aMILs vs aMILs plus vaccine. An evaluable patient is defined as one which has received the activated MILs and is at least 6 months post-transplant. Study Objectives: Disease response as determined by the Blade' criteria will be the primary endpoint of the trial at one year. Additional study endpoints include progression free survival, parameters of T cell reconstitution, anti-tumor immune responses as well as the effect on osteoclastogenesis and clonogenic myeloma precursor cells.

Conditions

Multiple Myeloma

Keywords

multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Response Rates by Blade Criteria

  Number of participants with each disease response category utilizing the Blade criteria: * Complete Response (CR): Defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells. * Near Complete Response (nCR): Defined as negative serum and urine paraprotein, positive serum and/or urine immunofixation, and a bone marrow aspirate with \< 5% plasma cells. * Very Good Partial Response (VGPR): Defined as negative serum and urine paraprotein with positive serum and/or urine immunofixation; or a 90% decrease in serum paraprotein with urine paraprotein \< 100 mg/24 hours. * Partial Response (PR): Defined as a 50-89% decrease in serum paraprotein. * Minimal Response (MR): Defined as a 25-49% decrease in serum paraprotein. * Stable Disease (SD): Defined as not falling into any other response category. * Overall response rate (ORR): Total of CR, nCR, VGPR, and PR.

  Up to 1 year

Secondary Outcomes (10)

• Progression-free Survival

  Up to 5 years

• Overall Survival

  Up to 5 years

• Feasibility as Measured by Participant Withdrawal or Removal

  Up to 1 year

• Safety as Measured by Grade 3-5 Adverse Events

  Up to 1 year

• Anti-tumor Immune Response

  Days 60, 180, and 360

Study Arms (2)

ASCT + MILs

EXPERIMENTAL

Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4.

Biological: Activated marrow infiltrating lymphocytes; Drug: Cyclophosphamide; Biological: Filgrastim; Procedure: Leukapheresis; Drug: Melphalan; Biological: Autologous stem cell transplant

ASCT + MILs + vaccine

EXPERIMENTAL

Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300.

Biological: Activated marrow infiltrating lymphocytes; Biological: Allogeneic Myeloma Vaccine; Drug: Cyclophosphamide; Biological: Filgrastim; Procedure: Leukapheresis; Drug: Melphalan; Biological: Autologous stem cell transplant

Interventions

Activated marrow infiltrating lymphocytes BIOLOGICAL

Administered on Days 3 and 4.

Also known as: MILs, aMILs

ASCT + MILs; ASCT + MILs + vaccine

Allogeneic Myeloma Vaccine BIOLOGICAL

Allogeneic granulocyte macrophage colony-stimulating factor (GM-CSF)-based myeloma cellular vaccine. Administered on Days 21, 60, 180, and 300.

ASCT + MILs + vaccine

Cyclophosphamide DRUG

Administered at 2.5 g/m\^2.

Also known as: Cytoxan

ASCT + MILs; ASCT + MILs + vaccine

Filgrastim BIOLOGICAL

Administered post cyclophosphamide daily until leukapheresis.

Also known as: G-CSF

ASCT + MILs; ASCT + MILs + vaccine

Leukapheresis PROCEDURE

Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.

Also known as: Apheresis

ASCT + MILs; ASCT + MILs + vaccine

Melphalan DRUG

100 mg/m\^2/day given on Days -2 and -1.

Also known as: Alkeran

ASCT + MILs; ASCT + MILs + vaccine

Autologous stem cell transplant BIOLOGICAL

Infused on Day 0.

Also known as: ASCT

ASCT + MILs; ASCT + MILs + vaccine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Durie-Salmon Stage II or III multiple myeloma
• Newly diagnosed either prior to receiving treatment or having completed induction therapy
• Relapsed myeloma not previously transplanted within the past 5 years
• Measurable serum and/or urine M-protein from prior to induction therapy documented and available. A positive serum free lite assay is acceptable
• Age greater than 18 years old
• ECOG performance status of 0 - 2
• Meet all institutional requirements for autologous stem cell transplantation
• The patient must be able to comprehend and have signed the informed consent

You may not qualify if:

• Diagnosis of any of the following plasma cell disorders: POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[M-protein\] and skin changes) Non-secretory myeloma (no measurable protein on Serum Free Lite Assay)
• Plasma cell leukemia
• Amyloidosis
• Use of corticosteroids (glucocorticoids) within 21 days of pre-transplant vaccine or bone marrow collection
• Use of any myeloma-specific therapy other than lenalidomide within 21 days of pre-transplant vaccine
• In a complete remission at the time of bone marrow collection
• Infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of vaccination or bone marrow collection
• Participation in any clinical trial, within four weeks prior to vaccination or bone marrow collection on this trial, which involved an investigational drug or device
• History of malignancy other than multiple myeloma within five years of vaccination or bone marrow collection, except adequately treated basal or squamous cell skin cancer
• Active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis) requiring systemic treatment. Hypothyroidism without evidence of Grave's Disease or Hashimoto's thyroiditis is permitted
• Evidence of spinal cord compression at time of transplant

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

N(1)-methyl-2-lysergic acid diethylamide; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; Leukapheresis; Blood Component Removal; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; 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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytapheresis; Biological Therapy; Therapeutics; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Results Point of Contact

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

iborrell@jhmi.edu

4109554967

Study Officials

• Ivan Borrello, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2009
• First Posted: January 11, 2010
• Study Start: January 15, 2010
• Primary Completion: December 1, 2014
• Study Completion: June 1, 2020
• Last Updated: April 9, 2021
• Results First Posted: October 8, 2019

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)