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

Purpose

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.

Condition	Intervention	Phase
Hodgkin Disease Lymphoma, Non-Hodgkin Multiple Myeloma Mantle Cell Lymphoma	Drug: Leuprolide acetate depot (LAD) 11.25 mg 3 Month Drug: Matched placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Leuprolide Acetate to Enhance Immune Function Post-Autologous Stem Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Bone Marrow Transplantation Cancer Hodgkin Disease Lymphoma Multiple Myeloma

Drug Information available for: Leuprolide acetate

U.S. FDA Resources

Further study details as provided by Abbott:

Primary Outcome 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 ] [ Designated as safety issue: No ]
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 [ Time Frame: Month 6 prevaccination (baseline) and Month 7 postvaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: Month 6 prevaccination (baseline) and Month 7 postvaccination ] [ Designated as safety issue: No ]
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:

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) ] [ Designated as safety issue: No ]
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 [ Time Frame: Pretransplant and posttransplant (Month 12) ] [ Designated as safety issue: No ]
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.

Enrollment:	25
Study Start Date:	February 2006
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: LAD 11.25 mg 3 Month Depot Three intramuscular injections LAD 11.25 mg 3 Month treatment administered approximately 3 months apart.	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. Other Name: Lupron
Placebo Comparator: Placebo Comparator Three intramuscular injections of matched placebo administered approximately 3 months apart.	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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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).
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.
Must be seronegative for hepatitis C and HIV.
Must have received prior tetanus immunization
Must not have received prior KLH immunization.
Must have an ECOG performance status (PS) <= 1 or Karnofsky PS >= 70%.
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.
Must be more than 3 weeks from any prior surgery (except for central line placement) and have fully recovered from the effects of surgery.
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.
Must be able to return to the clinical site for follow-up visits.
Must be able to provide written consent.

Exclusion Criteria:

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).
Must not have a diagnosed or suspected schistosomiasis infection.
Must not have previously received hematopoietic stem cell transplantation.
Must not require a tandem transplant.
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.
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.
Must not have had prior mediastinal or sternal radiation.
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.
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.
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.
Must not be receiving or plan to receive palifermin (KGF).
Must not have a allergy to shellfish.
Must not have previously taken a GnRH analog within 18 months.
Must not be a woman who has undergone bilateral oophorectomy, or man with orchiectomy.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00275262

Locations

United States, Missouri

Saint Louis, Missouri, United States, 63110
United States, New York

New York, New York, United States, 10021
United States, North Carolina

Durham, North Carolina, United States, 27710
United States, Texas

Houston, Texas, United States, 77030

Sponsors and Collaborators

Abbott

Norwood Immunology Limited

M.D. Anderson Cancer Center

Dana-Farber Cancer Institute

More Information

Additional Information:

For the Lupron 11.25 mg 3 month Depot Package Insert, refer to this link: This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Kristof Chwalisz, Therapeutic Area Head, Abbott
ClinicalTrials.gov Identifier:	NCT00275262 History of Changes
Other Study ID Numbers:	L-BT04-093
Study First Received:	January 9, 2006
Results First Received:	February 5, 2010
Last Updated:	April 9, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Abbott:

Bone marrow transplantation
Hematopoietic stem cell transplantation
Hodgkin's disease
non-Hodgkin's lymphoma
multiple myeloma

Additional relevant MeSH terms:

Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases

Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Leuprolide
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 19, 2013