Vaccine Therapy in Treating Patients With Acute Lymphoblastic Leukemia

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Terminated

CT.gov ID

NCT00020670

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

28.3

Actual Duration (Months)

4.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: CD 40	Early Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 20, 2001

Actual Primary Completion Date :

Apr 1, 2003

Actual Study Completion Date :

Jul 1, 2003

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Rate Of Successful Vaccine Preparation [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.***