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

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia; Multiple Myeloma
• Intervention / Treatment: Drug: CIK cells; Drug: etoposide; Drug: bcnu; Drug: cyclophosphamide; Drug: gemcitabine; Drug: vinorelbine; Drug: melphalan

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Vepesid; VP-16; Eposin; Etopophos; Drug: bcnu; 15 mg/kg; Other Names: Carmustine; Drug: cyclophosphamide; 100 mg/kg; Other Names: Cytoxan; Endoxan; Neosar; Revimmune; Procytox; 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sally Arai
• Investigators: Principal Investigator: Sally Arai, Stanford University

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: May 18, 2007
• First Submitted That Met QC Criteria: May 18, 2007
• First Posted (Estimate): May 22, 2007

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: January 9, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Hematologic Neoplasms; Multiple Myeloma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Gemcitabine; Cyclophosphamide; Etoposide; Melphalan; Vinorelbine; Carmustine
• Other Study ID Numbers: IRB-00245; 95889 (Other Identifier: Stanford University Alternate IRB Approval Number); BMT173 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO