Post-transplant Autologous Cytokine-induced Killer (CIK) Cells for Treatment of High Risk Hematologic Malignancies

Study Overview
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Brief Summary
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The purpose of the study is to conduct a phase I study of adoptive immunotherapy with autologous, ex-vivo expanded cytokine-induced killer (CIK) cells to reduce the relapse rate in autologous stem cell transplant patients with high-risk hematologic malignancies.

Detailed Description
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Disease relapse remains the major cause of treatment failure in autologous stem cell transplantation for patients with high-risk disease. Relapse after autologous transplant is in part due to the persistence of residual cancer cells. Cellular immunotherapy using activated autologous effector cells to recognize and kill tumor targets in a minimal disease state after transplant is a strategy being explored to reduce relapse and improve survival. We hypothesize that cytokine-induced killer (CIK) cell-based immunotherapy can reduce the relapse rate after high-risk autologous stem cell transplantation by treating post-transplant minimal residual disease.

Official Title
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A Phase I Study of Post-transplant Autologous Cytokine-induced Killer (CIK) Cells for the Treatment of High-risk Hematologic Malignancies

Conditions
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Leukemia, Multiple Myeloma

Intervention / Treatment
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* Drug: CIK cells
* Drug: etoposide
* Drug: bcnu
* Drug: cyclophosphamide
* Drug: gemcitabine
* Drug: vinorelbine
* Drug: melphalan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 18 and 75 years of age, inclusive candidates for standard autologous SCT who are at high risk for relapse: Acute myelogenous leukemia (AML), high risk, in CR1 or beyond without a donor (CR1 defined as: normal bone marrow morphology, resolution of any previously abnormal karyotype, neutrophils > 1000/ul, platelets > 100,000/ul, independence from red cell transfusion, no evidence extramedullary leukemia) Hodgkin's lymphoma relapsed or refractory, with the presence of >= 1 adverse risk factor (Adverse risk factors are defined as stage IV involvement of the lung or bone marrow, constitutional symptoms, and the presence of more than minimal residual disease before the preparatory regimen) Multiple myeloma with high risk features with only single autologous transplant option. High risk features defined as IgA myeloma, B2M > 2.5 mg/ml with normal kidney function, complex karyotypes or isolated chromosome 13 abnormalities, standard-dose therapy > 12 months, or inability to achieve at least 50% reduction of plasma cells in the bone marrow or 50% reduction in the paraprotein concentration after initial induction chemotherapy prior to transplant. Patients must have ECOG performance status < 2 Patients must have adequate renal function with a serum creatinine of < 2 mg/dl or creatinine clearance > 50 ml/min. Patients must have adequate liver function with a total bilirubin < 2 mg/dl or transaminases < 3 times the upper limit of normal. Patients must have negative antibody serology for human immunodeficiency virus (HIV1 and 2) Adult women and minorities will be included. Patients with childbearing potential must use effective contraception. Patients must sign informed consent prior to initiation of any study-related treatments. Exclusion Criteria: ECOG performance status > 2 LVEF < 45% Pulmonary diffusion capacity < 50% predicted Total bilirubin > 2 mg/dl Creatinine > 2 mg/dl Pregnancy Patients positive for HIV Patients with engraftment failure at day 42 post transplant defined as failure to achieve a granulocyte count > 500/ul on 3 successive daily determinations and an unsupported platelet count of >= 50,000/ul by day 42 Patients with active, uncontrolled infection that is expected to continue beyond day 42-63. Patients who fail to collect sufficient quantities of stem cells (> 1.6 x 10^9 cells) during apheresis to support CIK cell expansion cultures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous Cytokine-induced Killer Cells<br> | Drug: CIK cells<br>* 2x10e8 cells/kg<br>* Other names: autologous cytokine-induced killer cells;Drug: etoposide<br>* 60 mg/kg<br>* Other names: VP-16;Drug: bcnu<br>* 15 mg/kg<br>* Other names: Carmustine;Drug: cyclophosphamide<br>* 100 mg/kg<br>* Other names: cytophosphane;Drug: gemcitabine<br>* 1250 mg/m2<br>* Other names: Gemzar;Drug: vinorelbine<br>* 30 mg/m2<br>* Other names: Navelbine;Drug: melphalan<br>* 200 mg/m2<br>* Other names: Melphalan hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To document the toxicities of infusion of autologous CIK cells |  | Day 42 post autologous stem cell transplant | 
| Measure freedom from progression (FFP) |  | 1 and 2 years post-transplant | 
| Measure event free survival |  | 1 and 2 years post-transplant | 
| Measure overall survival |  | 1 and 2 years post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure disease response |  | at day 40-60, day 90, day 180, and yearly |