Immuno-Augmentation With GM-CSF of Pneumococcal Vaccine in Chronic Lymphocytic Leukemia Patients

• ClinicalTrials.gov Identifier: NCT00323557
• Recruitment Status: Completed
• First Posted: May 9, 2006
• Results First Posted: May 2, 2012
• Last Update Posted: December 5, 2012
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: Bayer
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Study Description

Brief Summary:

The goal of this clinical research study is to see if Leukine(R) (sargramostim) improves the effectiveness of the pneumococcal vaccine, a medicine used to prevent pneumococcal pneumonia, in patients with chronic lymphocytic leukemia (CLL).

Condition or disease	Intervention/treatment	Phase
Leukemia	Drug: Sargramostim (GM-CSF); Biological: Pneumococcal Vaccine	Phase 2

Detailed Description:

Sargramostim (also commonly called granulocyte macrophage colony stimulating factor - GM-CSF) is a medication used to stimulate the bone marrow production of white blood cells before a stem cell transplant, after chemotherapy or after a bone marrow transplant. Pneumococcal vaccine is a medication used to prevent infections caused by a bacteria called Streptococcus pneumoniae.

If you have not had a gammaglobulins test (a test to measure immunity against certain infectious diseases) measured within three months before the study begins, then this blood test will be done before you receive any study medications.

Women who are able to have children must have a negative urine pregnancy test before starting treatment.

After consenting to this study, you will be randomly assigned (as in the toss of a coin) to receive treatment with sargramostim in addition to the pneumococcal vaccine or to receive pneumococcal vaccine alone (Prevnar).

• If you are randomized to vaccine plus sargramostim group, you will receive an injection of sargramostim at the same time you receive the pneumococcal vaccine.
• If you are randomized to the vaccine alone group, you will receive the pneumococcal vaccine on the first day.

Blood tests will be performed on the day of the pneumococcal vaccination, and 4 weeks, 12 weeks and 24 weeks after vaccination. Each of the blood tests will require about 4 teaspoons of blood. These blood tests will measure your immunity to pneumococcal infection.

If after 6 months of your first vaccination your body is not able to show immunity to pneumococcal infection, you will receive a second dose either pneumococcal vaccine plus sargramostim or pneumococcal vaccine alone. Your immunity will be checked again at 4 weeks, 12 weeks, and 24 weeks after this second dose. Only 4 teaspoon of blood will be required for the tests.

You may be removed from the study if you have a severe allergic reaction to the sargramostim and/or pneumococcal vaccine. The total maximum time you will be on this is study is 24 months.

This is an investigational study. Both of the medications used in this study are approved by the FDA. Up to 50 patients may be treated on this study. All will be enrolled at M.D. Anderson.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Immuno-Augmentation With GM-CSF in Patients Receiving Pneumococcal Vaccine While Undergoing Treatment for Advanced Chronic Lymphocytic Leukemia (CLL)
• Study Start Date: June 2004
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: May 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pneumococcal Vaccine + GM-CSF; Vaccine subcutaneously + GM-CSF (3 Doses of 250 mg subcutaneously) given either Pre Vaccine at Day -7, Day -1 and Day 0 (day of pneumococcal vaccine) or Post Vaccine given at Day 0, Day +3 and Day +7.	Drug: Sargramostim (GM-CSF); Starting with 3 doses of 250 micrograms subcutaneously, either pre or post vaccine. For pre vaccine, GM-CSF on days -7 (+ 1 day) and -3 (+ 1 day), in the week prior to vaccination for pre-vaccination immune priming; 3rd dose on the day of vaccination (day 0); and for post-vaccine GM-CSF given simultaneously on day of vaccination (day 0) and 2 more doses Day +3 and Day +7 after pneumococcal vaccine.; Other Names: Leukine; GM-CSF; Granulocyte macrophage colony stimulating factor -
Experimental: Pneumococcal Vaccine Alone; First vaccine dose subcutaneously, Day 0.	Biological: Pneumococcal Vaccine; Subcutaneously on Day 0; Other Name: Prevnar

Outcome Measures

Primary Outcome Measures :

1. Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine [ Time Frame: Baseline and at 1 month after vaccine. ]
   Response defined as 2-fold rise in anticapsular immunoglobulin G (IgG) when prevaccination titer is compared with levels post vaccination and with a final level of >0.5 ug/mL. Anti-pneumococcal immunoglobulin titers measured at baseline and 1 month after vaccine. Response determined by measuring serum IgG to capsular polysaccharides from 6 of the most common infecting serotypes of Streptococcus pneumoniae.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1) Patients in complete / partial remission or those with active Chronic lymphocytic leukemia (CLL) with Rai stage 0 to 4.

Exclusion Criteria:

1. Patients will not be entered while neutropenic (PMNs < 500 cells/mm3) or having received Rituximab within 6 months.
2. Patients will not be entered while febrile (Temperature > 38 degrees C) within 1 week.
3. Active infection.
4. Patients with known Human immunodeficiency virus (HIV) infection.
5. Known history of allergy to Granulocyte/ macrophage colony stimulating factor (GM-CSF) or pneumococcal vaccine.
6. Chemotherapy other than Campath, fludarabine, cyclophosphamide, in 4 weeks.
7. Patients who have previously received pneumococcal vaccine within the preceding 12 months.
8. Absolute lymphocyte count less than 500 cells/mm3.

Contacts and Locations

Locations

United States, Texas

UT MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Bayer

Investigators

• Principal Investigator: Amar Safdar, MD; M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Safdar A, Rodriguez GH, Rueda AM, Wierda WG, Ferrajoli A, Musher DM, O'Brien S, Koller CA, Bodey GP, Keating MJ. Multiple-dose granulocyte-macrophage-colony-stimulating factor plus 23-valent polysaccharide pneumococcal vaccine in patients with chronic lymphocytic leukemia: a prospective, randomized trial of safety and immunogenicity. Cancer. 2008 Jul 15;113(2):383-7. doi: 10.1002/cncr.23561.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00323557
• Other Study ID Numbers: 2003-0605
• First Posted: May 9, 2006
• Results First Posted: May 2, 2012
• Last Update Posted: December 5, 2012
• Last Verified: December 2012

Keywords provided by M.D. Anderson Cancer Center:

Chronic Lymphocytic Leukemia; Leukemia; Sargramostim; Pneumococcal Pneumonia; Pneumococcal Vaccine; Prevnar; GM-CSF; CLL

Additional relevant MeSH terms:

Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Molgramostim; Sargramostim; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents