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

Sponsor

Sally Arai (Other)

Overall Status

Completed

CT.gov ID

NCT00477035

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Multiple Myeloma	Drug: CIK cells Drug: etoposide Drug: bcnu Drug: cyclophosphamide Drug: gemcitabine Drug: vinorelbine Drug: melphalan	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

Mar 1, 2011

Actual Study Completion Date :

Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Autologous Cytokine-induced Killer Cells	Drug: CIK cells 2x10e8 cells/kg Other Names: autologous cytokine-induced killer cells Drug: etoposide 60 mg/kg Other Names: Eposin Etopophos Vepesid VP-16 Drug: bcnu 15 mg/kg Other Names: Carmustine Drug: cyclophosphamide 100 mg/kg Other Names: Endoxan Cytoxan Neosar Procytox Revimmune cytophosphane Drug: gemcitabine 1250 mg/m2 Other Names: Gemzar Drug: vinorelbine 30 mg/m2 Other Names: Navelbine Drug: melphalan 200 mg/m2 Other Names: Alkeran Melphalan hydrochloride

Arm

Intervention/Treatment

Experimental: Autologous Cytokine-induced Killer Cells

Drug: CIK cells

2x10e8 cells/kg

Other Names:

autologous cytokine-induced killer cells

Drug: etoposide

60 mg/kg

Other Names:

Eposin

Etopophos

Vepesid

VP-16

Drug: bcnu

15 mg/kg

Other Names:

Carmustine

Drug: cyclophosphamide

100 mg/kg

Other Names:

Endoxan

Cytoxan

Neosar

Procytox

Revimmune

cytophosphane

Drug: gemcitabine

1250 mg/m2

Other Names:

Gemzar

Drug: vinorelbine

30 mg/m2

Other Names:

Navelbine

Drug: melphalan

200 mg/m2

Other Names:

Alkeran

Melphalan hydrochloride

Outcome Measures

Primary Outcome Measures

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

Measure disease response [at day 40-60, day 90, day 180, and yearly]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.