Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Vaccines

Melphalan

Immunomodulating Agents

Heptavalent Pneumococcal Conjugate Vaccine

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

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.

MILs

PCV13

Ivan Borrello, MD

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.

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.

Activated White Blood Cells With ASCT for Newly Diagnosed Multiple Myeloma

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

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

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.

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

Survival in months for participants who are alive (Overall Survival) and alive without disease progression (Progression-free survival). Disease progression is defined as a change from negative to positive on immunofixation or electrophoresis for participants previously in complete remission or a 25% increase in serum electrophoresis for participants not previously in complete remission. 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.

CRM-197 Prevnar-specific vaccine responses that measure the T-cell response of the vaccine quantified as %CD3+/CFSE-low/IFN-gamma+.

Myeloma lysate response that measures the T-cell response quantified as %CD3+/CFSE-low/IFN-gamma+.

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Per protocol, only adverse events (AEs) that were attributed to the study product (MILs) were collected and reported. AEs were collected daily through the date of engraftment, weekly through Day 28, and then at Days 60, 180, and 360.

ASCT+MILs

therapeutic autologous lymphocytes

therapeutic tumor infiltrating lymphocytes

melphalan

autologous hematopoietic stem cell transplantation

MILs in Patients Undergoing an Autologous Peripheral SCT

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Hematopoietic Engraftment

Complete Response

Partial Response

Stable Disease

Progressive Disease

Disease Response

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

Day 14

Day 28

Day 60

Day 180

Day 360

Data was not collected on one participant at the Day 28 and 180 timepoints, and data was not collected for eight participants at the Day 360 timepoint. Data was not collected on CD3+/CD4+/CD8+ cells for all participants.

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

Overall survival

Progression-free survival

Survival

At time of bone marrow harvest

Day 60 post-transplant

Day 180 post-transplant

Day 360 post-transplant

Pneumococcal-specific Vaccine Responses

Anti-tumor Immune Responses

Collection of MILs

Generation of MILs Product

Administration of ASCT+MILs

Symptoms and General Pathology

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphatic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Group A CLL patients: Previously immunized with PCV13, in this study receiving PCV13 followed by PPSV23

Group B CLL patients: Previously immunized with PPSV23, in this study receiving PCV13 followed by PCV13

Group C controls: Previously immunized with PCV13, in this study receiving PCV13

Group C controls: Previously immunized with PPPSV23, in this study receiving PCV13

Pneumococcal polysaccharides conjugated to CRM197 carrier protein

PPSV23

Bertil Uggla, Md, PhD

A randomized, multi-centre trial was conducted between 2013-2016, including 128 patients with untreated CLL from eight hematological clinics in Sweden. Vaccination with polysaccharide pneumococcal vaccine (PPSV23) or conjugated pneumococcal vaccine (PCV13) was performed and the results were published 2018. PCV13 showed a superior immune response, measured as OPA (opsonophagocytic assays) and ELISA (enzyme-linked immunosorbent assay), compared to PPSV23. Immune cells analyses after primary immunization will be performed. Between 2019-2021 a prospective follow up study was conducted of the same cohort and also included a control group. The study participants have been revaccinated with pneumococcal vaccines with the aim to evaluate the effect of repeated dose of PCV13. The antibody response (measured as titer with FMIA (fluorescent multiplexed bead-based immunoassay) and antibody function with MOPA (multiplexed opsonophagocytic assay) will be performed. Studies investigating the dynamics of immune cells before and after primary immunization and revaccination will be performed.

The study will give important answers about the optimal vaccination strategy in patients with CLL and can improve the vaccination recommendations in immunocompromised patients.

Chronic lymphocytic leukemia (CLL) patients have increased risk of pneumococcal infection due to defect T-cells, complements and neutrophil/monocyte function or hypogammaglobulinaemia. Side effects of different treatment modalities add further risk of infection.

Two pneumococcal vaccines are available, non-conjugated pneumococcal polysaccharide vaccines (PPSVs) and protein-conjugated vaccines (PCVs). 23-valent Pneumovax (PPSV23) has been recommended for healthy adults to protect against invasive pneumococcal disease (IPD) in Sweden and other countries for \>30 years. Patients with reduced adaptive immune function respond inadequately to PPSVs. Instead, the 13-valent Prevenar (PCV13) is recommended for a thymus-dependent immunological memory, yielding increased and persistent immune response .

In 2016, Swedish recommendations on pneumococcal vaccination of risk groups were updated, recommending PCV13 plus PPSV23 after \>8 weeks, but only after individual assessment. The evidence in CLL patients is limited but the Swedish CLL-Group has adopted the recommendations. The two vaccines are administrated consecutively to broaden the protection of additional serotype. If previously PPSV23 vaccinated, the PCV13 should be given \>12 months after PSV23 to avoid decreasing antibodies, i.e hyporesponse, but this is not studied in CLL patients.

Between 2013-2016, the investigators conducted a phase III trial at 8 hematological clinics in Sweden, including 126 untreated CLL patients, randomized to PCV13 (n=63) or PPSV23 (n=63) . The immune response was analyzed in terms of antibody induction and functionality, measured by enzyme-linked immunosorbent assay (ELISA) and opsonophagocytosis assay (OPA), respectively. The proportion of responding patients was larger for PCV13 than for PPSV23 after 4 weeks (40% vs. 22%, p=0.03) and 6 months (33% vs. 17%, p=0.04).

This study aims to investigate the persistent antibody protection in CLL patients 4-6 years after vaccination with PCV13 (n=63) vs PPSV23 (n=63), and the effect of revaccination with PCV13 in both groups. Also, the aim is to study if a repeated dose of PCV13 results in improved response, similar to controls after one dose of PCV13, and compared to PCV13 plus PPSV23 revaccination. Secondly, the study investigates the effect of pneumococcal vaccination on incidence of pneumococcal infection and colonization. A control group (N=32) has been included. Peripheral blood mononuclear cell (PBMC) have been collected and further studies on the dynamics of immune cells and cytokines before and after primary immunization and revaccination with polysaccharide vaccines and conjugated vaccines will be investigated.

A sub study was initiated february 2021 in the same cohort for sampling after vaccination against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the same study cohort, enabling comparison of immune response after administrating mRNA (messenger ribonucleic acid) vaccines.

Immune Response After Pneumococcal Vaccination in Patient With Chronic Lymphocytic Leukemia

Long Term Effect on Immune Response After Pneumococcal Vaccination in Patients With Chronic Lymphocytic Leukemia and Evaluation of the Effect of Revaccination

The long-term immune response, comparing the two vaccines PCV13 and PPSV23, 3-5 years after vaccination, measured as the proportion of subjects with a positive vaccination response in each of the two groups. A positive vaccination response is defined as a post vaccination OPA titer ≥ (LLOQ) in 8 of the 12 serotypes common for PCV13 and PPSV23 in serum collected

The change in immune response 8,16 and 52 weeks after first revaccination with PCV 13 (followed by a second revaccination, 8 weeks after first revaccination, with either PPSV23 (group A) or PCV13 (group B). Immune response is measured as the proportion of subjects with a positive vaccination response pre- and post- revaccination.

To study the incidence of pneumococcal colonization by naso-pharyngeal culturing nasopharyngeal swabs at inclusion after 8 weeks, 16 weeks and 12 months.

Dynamics of T- and B-cell subsets before and after revaccination will be explored using flow cytometry to determine the proportions of different B- and T-cell subsets

Antibody titers measured with FMIA regarding pneumococcal antibodies and Diasorins SARS-CoV-2 TrimericS IgG test (COV2TG) regarding Covid-19 antibodies, comparing antibody response to polysaccharide vaccine, conjugated vaccine and mRNA vaccine

To determine the incidence of IPD among the study participants by collecting data from medical records

Investigate the dynamics of cytokine levels before and after revaccination determined by multiplex immunoassays

Dynamic of T- and B-cell subsets before and after vaccination with polysaccharide vaccine, conjugated vaccine and mRNA vaccine using flow cytometry

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Activated White Blood Cells With ASCT for Newly Diagnosed Multiple Myeloma	NCT00566098	Multiple Myelom...	MILs Melphalan PCV13	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Activated White Blood Cells With ASCT for Newly Diagnosed Multiple Myeloma	NCT00566098	Multiple Myelom...	MILs Melphalan PCV13	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Immune Response After Pneumococcal Vaccination in Patient With Chronic Lymphocytic Leukemia	NCT05316831	CLL Vaccine Respons...	PCV13 PPSV23	18 Years -	Region Örebro County

Spots Global Cancer Trial Database for pcv13

Every month we try and update this database with for pcv13 cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for pcv13

Every month we try and update this database with for pcv13 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pcv13 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.