Host Dendritic Cells in Allograft Patients

Study Overview
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Brief Summary
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The purpose of this study is to assess preliminary efficacy and to determine the safety and feasibility of ex vivo generated dendritic cell (HDC) infusion with and without donor lymphocyte infusion (DLI) after allogeneic stem cell transplant (SCT). We also wish to establish the feasibility of apheresis shipment as well as vaccine shipment and stability in the population.

Official Title
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A Phase I Trial of Host Dendritic Cell Infusion After Allogeneic Stem Cell Transplant for Prevention or for Treatment of Relapsed Disease in Patients With Advanced Hematologic Malignancies

Conditions
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Relapsed Non-Hodgkin's Lymphoma, Hodgkin's Disease, Multiple Myeloma, Chronic Lymphocytic Lymphoma

Intervention / Treatment
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* Biological: MSSM/BIIR HDC Vax-001 (Host Dendritic Cells)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 Ability to sign informed consent ECOG performance status ≤3 Life expectancy > 6 months Adequate cardiac function: MUGA or Echocardiogram demonstrating >50% Ejection Fraction Adequate pulmonary function with DLCO > 50% Adequate hepatic function Bilirubin ≤ 1.5mg/dl Alkaline phosphatase ≤5 times the upper limit of normal Aspartate aminotransferase (AST) or serum glutamic-oxaloacetic transferase (SGOT) ≤ 3 times the upper limit of normal Alanine aminotransferase (ALT) or serum glutamic pyruvic transaminase (SGPT) ≤ 3 times the upper limit of normal Adequate renal function Estimated creatinine clearance > 40ml/min Diagnosis of one of the following Non-Hodgkin's lymphoma excluding Follicular lymphoma and Marginal Zone Lymphoma Hodgkin's lymphoma Multiple myeloma Chronic lymphocytic leukemia Eligible for allogeneic stem cell transplant with identified HLA-identical sibling (6/6 HLA match) or volunteer unrelated donor (8/8 allele HLA-matched (A, B, Cw, DRB1) Women of childbearing potential must have a negative serum pregnancy test prior to enrollment Women of childbearing potential must use effective means of birth control throughout the study. Men should not father a child while enrolled in the study. Effective means of birth control include condom, vasectomy or abstinence. Exclusion Criteria: Malignancies other than melanoma within five years of study entry, except carcinoma in-situ of the cervix or basal/squamous cell skin cancers Concurrent illnesses that would preclude survival > 6 months other than the disease under study Pregnancy or nursing HIV infection Treatment with prior donor lymphocyte infusion Prior allogeneic stem cell transplant History of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and thyroiditis Active infections including fungal infections and viral hepatitis GVHD greater than grade I GVHD of the skin Patient Exclusion Criteria for Part B (post Stem Cell Transplant) Malignancies other than melanoma within five years of study entry, except carcinoma in-situ of the cervix or basal/squamous cell skin cancers Concurrent illnesses that would preclude survival > 6 months other than the disease under study. Pregnancy or nursing HIV infection Treatment with prior donor lymphocyte infusion Prior allogeneic stem cell transplant More than 4 prior relapses History of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and thyroiditis Active infections including fungal infections and viral hepatitis GVHD greater than grade I GVHD of the skin No cytotoxics will be given within 4 weeks of administration of the investigational cell therapy Patients cannot receive any investigational agents within 30 days prior to administration of the investigational cell therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Patients with Minimal Residual Disease or Minimal Volume Relapse post allogeneic stem cell transplant will receive MSSM/BIIR HDC Vax-001 (Host Dendritic Cells) by infusion | Biological: MSSM/BIIR HDC Vax-001 (Host Dendritic Cells)<br>* Patients who have minimal residual disease or minimal volume relapse, and are at least four weeks post immunosuppression following allogeneic stem cell transplantation will receive a series of four HDC infusions (100,000 HDC/kg per infusion, one every four weeks(group 1). Those patients who have greater than minimal residual disease will receive HDC infusions, one every four weeks in conjunction with donor lymphocyte infusion (DLI) (group 2).<br>|
| Experimental: Group 2<br>Patients with greater than Minimal Residual Disease or Minimal Volume Relapse post allogeneic stem cell transplant will receive MSSM/BIIR HDC Vax-001 (Host Dendritic Cells) by infusion in conjunction with donor lymphocyte infusion (DLI) | Biological: MSSM/BIIR HDC Vax-001 (Host Dendritic Cells)<br>* Patients who have minimal residual disease or minimal volume relapse, and are at least four weeks post immunosuppression following allogeneic stem cell transplantation will receive a series of four HDC infusions (100,000 HDC/kg per infusion, one every four weeks(group 1). Those patients who have greater than minimal residual disease will receive HDC infusions, one every four weeks in conjunction with donor lymphocyte infusion (DLI) (group 2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of severe graft versus host disease (GVHD) grade C or D as defined by IBMTR grading. |  | 2 weeks following each HDC infusion and 4, 6 and 8 weeks after the last HDC infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of grade A and B acute GVHD, limited chronic GVHD, infusion reactions, graft loss and donor chimerism |  | 2 weeks following each HDC infusion and 4, 6 and 8 weeks after the last HDC infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed Non-Hodgkin's Lymphoma, Hodgkin's Disease, Multiple Myeloma, Chronic Lymphocytic Lymphoma, Relapsed Non-Hodgkin's lymphoma (excluding follicular lymphoma and marginal zone lymphoma)