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

NCT00275262 | Terminated Phase 2 Results

• 1 other identifier: L-BT04-093
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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.

  Month 6 prevaccination (baseline) and Month 7 postvaccination

• 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.

  Month 6 prevaccination (baseline) and Month 7 postvaccination

• 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.

  Month 6 prevaccination (baseline) and Month 7 postvaccination

Secondary Outcomes (2)

• 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)

• 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)

Study Arms (2)

LAD 11.25 mg 3 Month Depot

EXPERIMENTAL

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

Placebo Comparator

PLACEBO COMPARATOR

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

Drug: Matched placebo

Interventions

Leuprolide acetate depot (LAD) 11.25 mg 3 Month DRUG

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.

Also known as: Lupron

LAD 11.25 mg 3 Month Depot

Matched placebo DRUG

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.

Placebo Comparator

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abbott: lead
• Norwood Immunology Limited: collaborator
• M.D. Anderson Cancer Center: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (4)

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

New York, New York, 10021, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Multiple Myeloma; Lymphoma, Mantle-Cell

Interventions

Leuprolide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Limitations and Caveats

The study was terminated early because of slow enrollment. For the primary endpoint, changes from baseline within each treatment group were analyzed. Between treatment group comparisons were not performed because the sample size was too small.

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 9, 2006
• First Posted: January 11, 2006
• Study Start: February 1, 2006
• Primary Completion: February 1, 2009
• Last Updated: May 6, 2010
• Results First Posted: May 6, 2010

Record last verified: 2010-04

Locations

US (4)