A Study to Evaluate the Ability of Lupron Depot to Enhance Immune Function Following Bone Marrow Transplantation

Official Title: “Leuprolide Acetate to Enhance Immune Function Post-Autologous Stem Cell Transplantation”

Phase 2 study, conducted in patients with Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or mantle cell lymphoma undergoing high-dose chemotherapy and autologous stem cell transplantation.

This Phase 2 study will be conducted in patients with Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or mantle cell lymphoma undergoing high-dose chemotherapy and autologous stem cell transplantation. Patients will be randomized to receive either LAD 11.25 mg 3 Month treatment or placebo and all patients will be vaccinated with KLH 6 months posttransplant. Patients will be evaluated to determine if the rate of immunologic recovery in the LAD group is enhanced compared with the placebo group.

Intervention(s) in this Clinical Trial

• Drug: Leuprolide acetate depot (LAD) 11.25 mg 3 Month
  • LAD intramuscular injection 11.25 mg, 3 month duration. To stimulate immune response, a subcutaneous key limpet hemocyanin (KLH) vaccination injection (1 mg) was administered at Month 6.
• Drug: Matched placebo
  • Matched placebo intramuscular injection, 3 month duration. To stimulate immune response, a subcutaneous key limpet hemocyanin (KLH) vaccination injection (1 mg) was administered at Month 6.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: LAD 11.25 mg 3 Month Depot
  • Three intramuscular injections LAD 11.25 mg 3 Month treatment administered approximately 3 months apart.
• Placebo Comparator: Placebo Comparator
  • Three intramuscular injections of matched placebo administered approximately 3 months apart.

Primary Measures

• Mean Change From Baseline in IgM Response (Mcg/mL) Before Keyhole Limpet Hemocyanin (KLH) Vaccination at Month 6 and After KLH Vaccination at Month 7 in Patients Who Received LAD or Placebo
  • Time Frame: Month 6 prevaccination (baseline) and Month 7 postvaccination
    Safety Issue?: No
• Mean Change From Baseline in IgG1 Response (Mcg/mL) Before KLH Vaccination at Month 6 and After KLH Vaccination at Month 7 in Patients Who Received LAD or Placebo
  • Time Frame: Month 6 prevaccination (baseline) and Month 7 postvaccination
    Safety Issue?: No
• Mean Change From Baseline in Interferon Gamma Response (Spots/1 Million Cells) Before KLH Vaccination at Month 6 and After KLH Vaccination at Month 7 in Patients Who Received LAD or Placebo
  • Time Frame: Month 6 prevaccination (baseline) and Month 7 postvaccination
    Safety Issue?: No

Secondary Measures

• Mean Change From Baseline in T Cell Excision Circles (TREC) Per 100,000 CD4+ Cells to Final Visit in Patients Treated With LAD (11.25 mg) or Placebo After Transplant
  • Time Frame: Pretransplant and posttransplant (Month 12)
    Safety Issue?: No
• Mean Change From Baseline in TREC Per 100,000 CD8+ Cells to Final Visit in Patients Treated With LAD (11.25 mg) or Placebo After Transplant
  • Time Frame: Pretransplant and posttransplant (Month 12)
    Safety Issue?: No

Inclusion Criteria:

• 1. Must be female between the ages of 18 - 50 or if female > 50 years old have an estradiol concentration level >= 30 pg/mL and follicle stimulating hormone level < 40 mIU/mL, or male between the ages of 18-65 (inclusive).
• 2. Must have Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or mantle cell lymphoma and be considered an appropriate candidate for hematopoietic stem cell transplant.
• 1. Multiple myeloma patients should have had a partial or complete response to chemotherapy.
• 2. Patients with Hodgkin's disease or non-Hodgkin's lymphoma who achieve a partial response to initial chemotherapy or first or second chemosensitive relapse, achieving a complete or partial response to salvage treatment. Patients in first remission with mantle cell lymphoma, or with intermediate or high grade lymphoma, presenting with high intermediate or high IPI (International
• Prognostic Index) scores are also eligible.
• 3. Must be seronegative for hepatitis C and HIV.
• 4. Must have received prior tetanus immunization
• 5. Must not have received prior KLH immunization.
• 6. Must have an ECOG performance status (PS) <= 1 or Karnofsky PS >= 70%.
• 7. Must have creatinine <= 2.0 mg/dL; ejection fraction > 45%; carbon monoxide diffusion in the lungs (DLCO) > 50% of predicted; serum bilirubin < 1.5 times the upper limit of normal unless Gilbert's syndrome, SGPT < 3 times normal value.
• 8. Must be more than 3 weeks from any prior surgery (except for central line placement) and have fully recovered from the effects of surgery.
• 9. Must have an absolute neutrophil count (ANC) >= 1,500 µL, platelet count >= 100,000/µL and hemoglobin >= 8.0 gm/dL within 21 days prior to randomization.
• 10. Must be able to return to the clinical site for follow-up visits.
• 11. Must be able to provide written consent.

Exclusion Criteria:

• 1. Must not have an uncontrolled life-threatening infection (or active infectious process requiring intravenous [IV] systemic medical therapy within 1 week prior to study enrollment).
• 2. Must not have a diagnosed or suspected schistosomiasis infection.
• 3. Must not have previously received hematopoietic stem cell transplantation.
• 4. Must not require a tandem transplant.
• 5. Must not be female with a positive pregnancy test, pregnant, or lactating and breast feeding, or wish to become pregnant during the course of the study. Must agree to use barrier method of contraception.
• 6. Must not be receiving estrogen or testosterone replacement therapy,phytoestrogen, phyto-testosterone, or oral contraceptives (patients may enroll if oral contraceptives are ceased prior to study entry), or have been administered Depo
• Provera within 3 months of entering the study.
• 7. Must not have had prior mediastinal or sternal radiation.
• 8. Must not have received any investigational drug other than antibiotics within 3 weeks prior to study drug administration or are scheduled to receive an investigational drug during the course of this study.
• 9. Must not have unstable cardiac arrhythmias, uncontrolled congestive heart failure, history of myocardial infarction (MI) or ischemia, stroke, or embolic events within 6 months before study start.
• 10. Must not have medical or psychiatric conditions that, in the opinion of the investigator, would compromise the patient's ability to participate in the study.
• 11. Must not be receiving or plan to receive palifermin (KGF).
• 12. Must not have a allergy to shellfish.
• 13. Must not have previously taken a GnRH analog within 18 months.
• 14. Must not be a woman who has undergone bilateral oophorectomy, or man with orchiectomy.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Abbott Industry

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00275262

Study ID Number: L-BT04-093

ClinicalTrials.gov Identifier: NCT00275262

Health Authority: United States: Food and Drug Administration

For the Lupron 11.25 mg 3 month Depot Package Insert, refer to this link: