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Immunotherapy for Asymptomatic Phase Lymphoplasmacytic Lymphoma

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ClinicalTrials.gov Identifier: NCT01209871
Recruitment Status : Active, not recruiting
First Posted : September 27, 2010
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of a cancer vaccine that can be given to patients with asymptomatic lymphoplasmacytic lymphoma (LPL). The safety of this vaccine is also being studied.

This is an investigational study. The vaccine is not FDA approved or commercially available. It is currently being used for research purposes only.

Up to 12 patients will take part in this study. All patients will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Lymphoma Lymphoplasmacytic Lymphoma Waldenström Macroglobulinemia Biological: DNA Vaccine Phase 1

  Hide Detailed Description

Detailed Description:

The Study Vaccine:

The cancer vaccine used in this study is made from DNA (the genetic material of cells). The vaccine is designed to increase your immune system's ability to react against lymphoplasmacytic lymphoma.

Making the Vaccine:

About 12 months are needed to make this vaccine from your tumor. Although a lot of effort will be used to try to make the vaccine for each participant, researchers are not always successful. Researchers cannot and do not guarantee that you will receive a vaccine.

Baseline Procedures:

The following tests and procedures will be performed within 4 weeks before starting the vaccine:

  • Your medical history will be recorded (+/- 2 days).
  • You will have a physical exam (+/- 2 days).
  • You will be asked about any drugs you may be taking.
  • Blood (about 1 tablespoon) will be collected for routine tests. This routine blood draw will include a pregnancy test for women who are able to become pregnant. To take part in this study, you must not be pregnant.
  • Blood (about 1 tablespoon) and urine will be collected to check the status of the disease. This urine will be collected over a 24-hour period. You will be provided with a container for urine collection.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will be assigned to a dose level based on when you start the study. If you are one of the first 3 participants, you will receive a lower dose of the vaccine. If that dose level is found to be safe, all other participants will receive a higher dose of vaccine.

Once the vaccine is ready (about 12 months), you may receive up to 3 vaccines, given one month apart. The vaccine will be given using a needle free injection device that works by delivering the vaccine through your skin. Each dose of vaccine will be split between 5 separate injections. You will no longer be able to take the vaccine if the disease gets worse or intolerable side effects occur. Your participation on this study will be complete 1 year after your last vaccination.

Study Visits:

During the study, you will have the following tests and procedures performed. These tests and procedures are part of regular cancer care; however, they will be done more often while you are in this study.

In the 7 days before the first vaccine, if your doctor thinks it is needed, you may have a CT scan to check the status of the disease.

Within 2 days before each vaccine:

  • Blood (about 5 tablespoons) will be drawn for routine tests.
  • Blood (about 1 teaspoon) and urine will be collected to check the status of the disease. This urine will be collected over a 24-hour period. You will be provided with a container for urine collection.
  • Blood (about 2 teaspoons) will be drawn to check for immune system disorders.

On the day you receive your vaccine:

  • You will have a physical exam.
  • You will be asked how you are feeling.
  • You will be asked about any drugs you may be taking.

At 4 and 8 weeks, blood (2 tablespoons) will be drawn to check how your immune system responds to the vaccines.

At 4 weeks after your last vaccination:

  • Blood (up to 8 tablespoons) will be drawn for testing of cytokines (proteins that may affect the immune system), to check the status of the disease, and to check how your immune system responds to the vaccines and to your body's own proteins.
  • You will have a bone marrow aspiration to check the status of the disease.

About 4 weeks after your last vaccination, and then every 2 month for 1 year:

  • Your medical history will be recorded.
  • You will have a physical exam.
  • You will be asked how you are feeling.
  • You will be asked about any drugs you may be taking.
  • Blood (about 1 tablespoon) will be drawn for routine tests.
  • Blood (about 1 tablespoon) and urine will be collected to check the status of the disease. This urine will be collected over a 24-hour period. You will be provided with a container for urine collection.
  • Blood (about 2 teaspoons) will be drawn to check for immune system disorders.

About 4 months after your last vaccination, and then every 4 months for 1 year, blood (about 4 tablespoons) will be drawn to check how your immune system responds to the vaccines.

About 4 weeks after your last vaccination, and then every 6 months for 1 year, you will have a CT scan to check the status of the disease.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of an Active Immunotherapy for Asymptomatic Phase Lymphoplasmacytic Lymphoma With DNA Vaccines Encoding Antigen-Chemokine Fusion
Actual Study Start Date : February 26, 2015
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2021


Arm Intervention/treatment
Experimental: Cohort 1 - DNA Vaccine

Series of 3 autologous lymphoma immunoglobulin derived scFV-chemokine DNA vaccinations.

Cohort 1 dose 500 μg intramuscularly at 4-week intervals (+/- 3 business days) according to the following schedule: 0, 4, and 8 weeks.

Biological: DNA Vaccine
Series of 3 autologous lymphoma immunoglobulin derived scFV-chemokine DNA vaccinations (Cohort 1 dose 500 μg; Cohort 2 dose 2500 μg) intramuscularly at 4-week intervals (+/- 3 business days) according to the following schedule: 0, 4, and 8 weeks.
Other Names:
  • plasmid DNA
  • lymphoma DNA vaccine
  • lymphoma immunoglobulin derived scFV-chemokine DNA vaccinations

Experimental: Cohort 2 - DNA Vaccine

Series of 3 autologous lymphoma immunoglobulin derived scFV-chemokine DNA vaccinations.

Cohort 2 dose 2500 μg intramuscularly at 4-week intervals (+/- 3 business days) according to the following schedule: 0, 4, and 8 weeks.

Biological: DNA Vaccine
Series of 3 autologous lymphoma immunoglobulin derived scFV-chemokine DNA vaccinations (Cohort 1 dose 500 μg; Cohort 2 dose 2500 μg) intramuscularly at 4-week intervals (+/- 3 business days) according to the following schedule: 0, 4, and 8 weeks.
Other Names:
  • plasmid DNA
  • lymphoma DNA vaccine
  • lymphoma immunoglobulin derived scFV-chemokine DNA vaccinations




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of a Novel Lymphoma DNA Vaccine Encoding a MIP3a-Fused Lymphoma Idiotype [ Time Frame: 4 weeks ]
    MTD defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose-limiting toxicity (DLT).


Secondary Outcome Measures :
  1. Immune Response [ Time Frame: 12 weeks ]
    Immune response defined as at least a three-fold rise in the precursor frequency of tumor-reactive T cells in the post-vaccine PBMC sample at 12 weeks as compared to the pre-vaccine sample, with a minimum precursor frequency of 1 in 80,000 cells if the precursor frequency in the pre-vaccine sample is zero. Rate of immune response estimated.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >/= 18 years
  2. Tissue diagnosis of Lymphoplasmacytic Lymphoma with surface IgG, IgA or IgM phenotype with a monoclonal heavy and light chain as determined by flow cytometry. All primary diagnostic lymph node and/or bone marrow biopsies will be reviewed at the University of Texas M.D. Anderson Cancer Center (UTMDACC)
  3. Previously untreated patients with lymphoplasmacytic lymphoma (of any subtype: IgG, IgA, IgM) in the asymptomatic phase
  4. Patients must provide a lymph node sample of at least 1.5cm in the long axis, or a bone marrow aspiration sample providing at least 5 million CD20 and/or CD38+ (approximately 10 ml)
  5. ECOG performance status of 0 or 1
  6. Serum creatinine </= 1.5 mg/dl and a Creatinine clearance >/= 30 ml/min.
  7. Total Bilirubin </= 1.5 mg/dl unless felt secondary to Gilbert's disease and AST/ALT </= 2 x upper limit of normal
  8. Ability to provide informed consent, and to return to clinic for adequate follow-up for the period that the protocol requires
  9. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 30 days after the last vaccination has been administered.
  10. Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

  1. HIV, Hepatitis B and/or Hepatitis C infection
  2. Pregnancy or lactating females
  3. Patients with previous history of malignancy within the last 5 years except curatively treated squamous or basal cell carcinoma of the skin or curatively treated carcinoma in-situ of other organs
  4. Any medical or psychiatric condition that in the opinion of the principal investigator would compromise the patient's ability to tolerate this treatment
  5. Patients with New York Heart Association Class 3 or 4 disease
  6. Patients with a history of autoimmune diseases except for Hashimoto's thyroiditis
  7. Patients with positive ANA and/or anti-dsDNA antibodies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01209871


Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Sheeba K. Thomas, MD M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01209871     History of Changes
Other Study ID Numbers: 2009-0465
NCI-2012-01897 ( Registry Identifier: NCI CTRP )
First Posted: September 27, 2010    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Lymphoplasmacytic Lymphoma
Recombinant DNA
Fusion DNA Vaccine
Waldenström macroglobulinemia

Additional relevant MeSH terms:
Lymphoma
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Vaccines
Immunoglobulins
Antibodies
Immunologic Factors
Physiological Effects of Drugs