CpG 7909 in Treating Patients Who Have Undergone Autologous Stem Cell Transplant

OBJECTIVES:

Primary

- Determine whether CpG 7909 enhances immune function, as measured by the response to
keyhole limpet hemocyanin (neo-antigen) and tetanus toxoid (memory antigen), in patients
who have undergone autologous stem cell transplantation.

Secondary

- Determine if dose escalation of CpG 7909, within a range of previously tested safe doses
of CpG 7909, impacts upon the primary immune readouts.

OUTLINE: This is a non-randomized, dose-escalation study of CpG 7909.

Patients receive CpG 7909 subcutaneously (SC) on days 1, 7, and 14. Patients receive keyhole
limpet hemocyanin SC and tetanus toxoid SC on day 7.

Cohorts of 3-6 patients receive escalating doses of Cp6 7909 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. A total of 10 patients are treated at the MTD.

Blood is collected at baseline and at approximately day 40 for immunological studies,
including immunoenzyme techniques, antibody response assays, and immunophenotyping.

After completion of study treatment, patients are followed every 3 months for 1 year.

Inclusion Criteria:

- Patients must have undergone autologous transplantation for non-Hodgkin's lymphoma
(NHL), Hodgkin's disease, acute myelogenous leukemia (AML), germ cell tumors, or
multiple myeloma.

- Patients must be eligible for and consent to participate in study MT1999 06 -
Vaccination with tetanus toxoid and Keyhole Limpet Hemocyanin (KLH) to assess antigen
specific immune responses (BB-IND 10430).

- Patients will be eligible to receive CpG 7909 and vaccines on or after day 60 post
transplant. No patients are eligible for this protocol beyond day 74 post transplant.
Therefore, all patients will start therapy on this protocol between days 60-74 post
transplant to allow for patient scheduling flexibility.

- Patients must have engraftment and be independent of transfusion support or growth
factor support.

- Patients must not have received platelet or red-cell transfusions in the previous
week.

- Patients must have been continuously off all growth factors for at least 1 week.

- Unsupported counts must be:

- platelets ≥ 50,000/ml

- Hgb ≥ 9 gm/ul

- Absolute neutrophil count ≥ 1000/µL

- Absolute lymphocyte count ≥ 500/µL

- Patients must have a current performance status of 0-1 (Eastern Cooperative Oncology
Group) or 70-100% (Karnofsky.

- Patients must be afebrile, off antibiotics therapeutic (not prophylactic), and free of
evidence of active infection. Patients must be off intravenous (IV) hyperalimentation
and IV fluids.

- Minimum laboratory values within 2 weeks of entry: Creatinine ≤ 2.0 mg/dl or CrCl ≥ 50
ml/min, Bilirubin, ALT ≤ 2 x normal

- Age >18 years

- Patients receiving or scheduled to receive planned radiation therapy, growth factor
therapy, or steroid therapy during the study period will be ineligible. Patients must
have completed all planned post-transplant radiation therapy if applicable.

- Patients must be able to give written informed consent and agree to comply with the
study parameters

- Patients must agree to use contraception during the study.

Exclusion Criteria:

Patients with one or more of the following:

- Active infection, or fever >38.2˚C

- Significant nonmalignant disease including documented HIV infection, uncontrolled
hypertension (diastolic blood presses >115 mmHg), unstable angina, congestive heart
failure (NY Class II), poorly controlled diabetes, coronary angioplasty within 6
months, myocardial infarction with the last 6 months, or uncontrolled atrial or
ventricular cardiac arrhythmias.

- Hematopoietic growth factors administered within 1 week of study entry.

- Expected to require additional cytotoxic therapy within 30 days of study

- Receiving other post-transplant investigational agents

- Patients with a history of autoimmune diseases will be ineligible for this protocol

- It is unknown whether CpG 7909 may exacerbate autoimmune disorders by its
immunomodulatory effects. Therefore, subjects with a history of autoimmune disease
should not receive CpG 7909. Controlled thyroid disease is permissible.

- Systemic corticosteroids or other immunosuppressants

- Pregnant or lactating (It is unlikely and probably unwise that a women of childbearing
potential become pregnant this early after transplant, however; if any suspicion, a
pregnancy test should be done)

- Not meeting one or more of the eligibility criteria, as listed above