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

Primary Purpose

Hodgkin Disease, Lymphoma, Non-Hodgkin, Multiple Myeloma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Leuprolide acetate depot (LAD) 11.25 mg 3 Month
Matched placebo
Sponsored by
Abbott
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkin Disease focused on measuring Bone marrow transplantation, Hematopoietic stem cell transplantation, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. Multiple myeloma patients should have had a partial or complete response to chemotherapy. 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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

LAD 11.25 mg 3 Month Depot

Placebo Comparator

Arm Description

Three intramuscular injections LAD 11.25 mg 3 Month treatment administered approximately 3 months apart.

Three intramuscular injections of matched placebo administered approximately 3 months apart.

Outcomes

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
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
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
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
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
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.

Full Information

First Posted
January 9, 2006
Last Updated
April 9, 2010
Sponsor
Abbott
Collaborators
Norwood Immunology Limited, M.D. Anderson Cancer Center, Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00275262
Brief Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2010
Overall Recruitment Status
Terminated
Study Start Date
February 2006 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Abbott
Collaborators
Norwood Immunology Limited, M.D. Anderson Cancer Center, Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Disease, Lymphoma, Non-Hodgkin, Multiple Myeloma, Mantle Cell Lymphoma
Keywords
Bone marrow transplantation, Hematopoietic stem cell transplantation, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LAD 11.25 mg 3 Month Depot
Arm Type
Experimental
Arm Description
Three intramuscular injections LAD 11.25 mg 3 Month treatment administered approximately 3 months apart.
Arm Title
Placebo Comparator
Arm Type
Placebo Comparator
Arm Description
Three intramuscular injections of matched placebo administered approximately 3 months apart.
Intervention Type
Drug
Intervention Name(s)
Leuprolide acetate depot (LAD) 11.25 mg 3 Month
Other Intervention Name(s)
Lupron
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Matched placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Month 6 prevaccination (baseline) and Month 7 postvaccination
Title
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
Description
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.
Time Frame
Month 6 prevaccination (baseline) and Month 7 postvaccination
Title
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
Description
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.
Time Frame
Month 6 prevaccination (baseline) and Month 7 postvaccination
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Pretransplant and posttransplant (Month 12)
Title
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
Description
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.
Time Frame
Pretransplant and posttransplant (Month 12)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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. Multiple myeloma patients should have had a partial or complete response to chemotherapy. 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.
Facility Information:
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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

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