Vaccine Therapy in Treating Patients With Acute Lymphoblastic Leukemia

June 19, 2017 updated by: Nicholas Haining, MD, Dana-Farber Cancer Institute

A Phase I Study of Vaccination With Autologous CD40-Activated Acute Lymphoblastic Leukemia Cells

The prognosis for children and adults with acute lymphoblastic leukemia (ALL) has improved significantly over the years. Nevertheless, patients who experience disease relapse or induction failure along with patients having unfavorable genetics [t(4;11) or t(9;22)] have dismal prognosis. For these patients, novel therapeutic approaches such as immunotherapy are needed. In this clinical trial, investigators evaluate whether it is feasible to make a vaccine from leukemia cells and whether this vaccine enables direct immunity against cancer cells in patients.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES Primary

  • To determine feasibility of generating a cellular vaccine composed of CD40-activated autologous ALL cells
  • To determine feasibility of vaccine administration according to the proposed schedule
  • To determine toxicity of vaccination with CD40-activated autologous ALL cells

Secondary

  • To assess ALL-specific immunity following vaccination
  • To assess the generation of immunity to control antigens
  • To develop preliminary information on effect vaccination on tumor response

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  • B-cell acute lymphoblastic leukemia
  • Disease involving at least 30% of bone marrow or circulating blasts

  • In first relapse with at least 1 of the following high-risk features:

    • Age under 1 year at diagnosis
    • Age over 18 years at diagnosis
    • t(9;22)
    • Occurrence of first relapse less than 18 months after diagnosis
    • In second relapse or beyond
    • Refractory disease
  • Successful generation of adequate CD40 ligand-activated autologous tumor cell vaccine
  • Less than 1 year since tumor cell collection
  • Patients in first relapse or beyond must be ineligible for or have declined allogeneic bone marrow transplantation in order to receive study vaccine
  • Patients need not be in complete remission to receive study vaccine
  • Patients may have received an allogeneic hematopoetic stem cell transplant in the past
  • No chemotherapy, radiotherapy, immunotherapy or immunosuppressive treatment or within 3 weeks of vaccination
  • Adequate hepatic function as defined by: Bilirubin < 2x normal; AST < 3x normal; ALT < 6x normal
  • Adequate renal function defined by: Creatinine < 2x normal
  • <1 year since tumor cell collection

Exclusion Criteria

  • Concurrent treatment as part of another therapeutic research protocol
  • Pregnancy or nursing mothers
  • Clinically significant pulmonary or cardiac disease
  • Clinically significant autoimmune disease
  • Documented infection that is active and/or not responding to therapy
  • Evidence of HIV infection or known positive HIV serology
  • Lansky performance scale (if <18yo) <60%, Karnofsky performance scale (if >18yo) >60%
  • Once vaccination course has started: patients may not receive chemotherapy, radiotherapy, immunotherapy or immunosuppressive treatment, hematopoetic growth factors. However between tumor cell collection and vaccine administration, patients may receive non-protocol chemotherapy.

********************************************NOTE***************************************************

It is anticipated that there will be a number of patients at first relapse who are eligible for tumor cell collection and vaccine preparation but who are not eligible to receive the vaccination course. These patients will be evaluable for Objective 3.1.1 (feasibility of vaccine preparation). Patients at first relapse who are eligible for vaccine preparation but not administration should instead be treated with standard salvage regimens which may include allogeneic bone marrow transplantation according to the judgement of their primary oncologist. However, these patients represent a population at extremely high risk for progression of their disease following salvage therapy. Many of these patients will therefore be likely to fulfill eligibility criteria for vaccination in the future (i.e.

should they relapse again, or fail to enter 2nd complete remission). The majority of those patients who relapse for a second time will do so within 1 year. Those patients who become eligible for vaccination because of 2nd relapse within 1 year of tumor cell collection will receive the original vaccine and will not have further vaccine made from tumor cells collected at the time of 2nd relapse. Given the proliferative thrust of the disease in many patients, it will be advantageous to have vaccines already prepared for these patients to reduce the amount of time from 2nd relapse to vaccination.***

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CD40 Cell Vaccination
Patients will undergo tumor cell collection followed by vaccine preparation and then vaccination. Autologous acute lymphoblastic leukemia (ALL) cells are harvested, cultured with CD40 ligand, pulsed with keyhole limpet hemocyanin (KLH), and then irradiated to produce the vaccine. Patients receive either 1 x 10^7 or 1 x 10^8 CD40 cells/vaccination depending on the number of tumor cells obtained. Vaccinations are administered every two weeks as outpatient therapy. Evaluable patients receive the course of at least 4 vaccinations at weeks 0, 2, 4, 6. Patients may continue receiving vaccinations every 2 weeks if chemotherapy is not required for symptomatic disease.
Biological: CD 40
Other Names:
  • Autologous tumor cell vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate Of Successful Vaccine Preparation
Time Frame: 6 weeks
Vaccine preparation is a success if an adequate number of CD40 activated cells (at least 1 x 10^8 cells) can be generated.
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: W. Nicholas Haining, BM, BCh, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2001

Primary Completion (Actual)

April 1, 2003

Study Completion (Actual)

July 1, 2003

Study Registration Dates

First Submitted

July 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

June 20, 2017

Last Update Submitted That Met QC Criteria

June 19, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00-053
  • P30CA006516 (U.S. NIH Grant/Contract)
  • P01CA068484 (U.S. NIH Grant/Contract)
  • DFCI-00053
  • NCI-H01-0074

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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