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

Phase 2

Terminated

• Conditions: Hodgkin Disease; Lymphoma, Non-Hodgkin; Multiple Myeloma; Mantle Cell Lymphoma
• Interventions: Drug: Leuprolide acetate depot (LAD) 11.25 mg 3 Month; Drug: Matched placebo

• Registration Number: NCT00275262
• Lead Sponsor: Abbott

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2006-01-09
• Study First Submitted QC: 2006-01-10
• Study First Posted: 2006-01-11
• Study Start: 2006-02
• Primary Completion: 2009-02
• Results First Submitted: 2010-02-05
• Status Verified: 2010-04
• Results First Submitted QC: 2010-04-09
• Last Update Submitted: 2010-04-09
• Results First Posted: 2010-05-06
• Last Update Posted: 2010-05-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 25

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LAD 11.25 mg 3 Month Depot	Leuprolide acetate depot (LAD) 11.25 mg 3 Month	Three intramuscular injections LAD 11.25 mg 3 Month treatment administered approximately 3 months apart.
Placebo Comparator	Matched placebo	Three intramuscular injections of matched placebo administered approximately 3 months apart.

Primary Outcome Measures

Name	Time	Method
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	Month 6 prevaccination (baseline) and Month 7 postvaccination	Patients received a subcutaneous injection of KLH vaccine 1 month after subjects received the third injection of LAD or placebo. Serum immunoglobulin IgM antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Baseline is defined as the IgM concentration before the KLH vaccination. Change from baseline was calculated as the IgM value postvaccination minus the IgM value at prevaccination.
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	Month 6 prevaccination (baseline) and Month 7 postvaccination	Patients received a subcutaneous injection of KLH vaccine 1 month after subjects received the third injection of LAD or placebo. Serum immunoglobulin IgG1 antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Baseline is defined as the IgG1 concentration before the KLH vaccination. Change from baseline was calculated as the IgG1 value postvaccination minus the IgG1 value at baseline.
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	Month 6 prevaccination (baseline) and Month 7 postvaccination	Patients received a subcutaneous injection of KLH vaccine 1 month after subjects received the third injection of LAD or placebo. Interferon gamma was determined by enzyme-linked immunosorbent spot-forming cell (ELISpot). Baseline is defined as the interferon gamma concentration obtained before the KLH vaccination. Change from baseline was calculated as the interferon gamma value postvaccination minus the interferon gamma value at baseline.

Secondary Outcome Measures

Name	Time	Method
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	Pretransplant and posttransplant (Month 12)	CD4+ cells are a type of T cell. T cells are produced in the thymus and thymic function can be determined by TREC. By counting the number of TRECs present (only 1 copy per cell) within a population of CD4 cells, an assessment of T cell recovery and immune response is obtained. Mayo Medical Clinic. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/87959. Accessed 17 MARCH 2010; The change from baseline is defined as posttransplant TREC/100,000 CD4+ cells minus pretransplant TREC /100,000 CD4+ cells.
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	Pretransplant and posttransplant (Month 12)	CD8+ cells are a type of T cell. T cells are produced in the thymus and thymic function can be determined by TREC. By counting the number of TRECs present (only 1 copy per cell) within a population of CD8+ cells, an assessment of T cell recovery and immune response is obtained. Mayo Medical Clinic. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/87959. Accessed 17 MARCH 2010; The change from baseline is defined as posttransplant TREC/100,000 CD8+ cells minus pretransplant TREC /100,000 CD8+ cells.