Hodgkin Disease, Lymphoma, Non-Hodgkin, Mantle Cell Lymphoma, Multiple Myeloma
Conditions
Keywords
Bone marrow transplantation, Hematopoietic stem cell transplantation, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma
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.
Interventions
DRUGLeuprolide 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.
DRUGMatched 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.
Sponsors
Norwood Immunology Limited
M.D. Anderson Cancer Center
Dana-Farber Cancer Institute
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month Patients received 1 injection of LAD 11.25 mg every 3 months for a total treatment period of 9 months. | 12 |
| Placebo Patients received 1 injection of placebo every 3 months for a total treatment period of 9 months. | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Disease progression | 2 | 5 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Started Chemotherapy | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 12 Participants | 25 Participants |
| Age Continuous | 47.4 years STANDARD_DEVIATION 7.04 | 49.0 years STANDARD_DEVIATION 10.16 | 48.2 years STANDARD_DEVIATION 8.53 |
| Region of Enrollment United States | 13 participants | 12 participants | 25 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 12 | 7 / 13 |
| serious Total, serious adverse events | 6 / 12 | 4 / 13 |
Outcome results
Primary
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.
Time frame: Month 6 prevaccination (baseline) and Month 7 postvaccination
Population: Eight subjects from the LAD-treated arm and 5 subjects from the placebo-treated arm were assessed for IgG1. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Mean IgG1 at baseline (mcg/mL) | 8.6 mcg/mL | Standard Deviation 9.1 |
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Mean IgG1 change from baseline (mcg/mL) | 46.16 mcg/mL | Standard Deviation 44.01 |
| Placebo | 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 | Mean IgG1 at baseline (mcg/mL) | 10.8 mcg/mL | Standard Deviation 11.6 |
| Placebo | 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 | Mean IgG1 change from baseline (mcg/mL) | 16.76 mcg/mL | Standard Deviation 28.15 |
Primary
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.
Time frame: Month 6 prevaccination (baseline) and Month 7 postvaccination
Population: Eight subjects from the LAD-treated arm and 5 subjects from the placebo-treated arm were assessed for IgM. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Mean IgM at baseline (mcg/mL) | 4.0 mcg/mL | Standard Deviation 3.8 |
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Mean IgM change from baseline (mcg/mL) | 2.91 mcg/mL | Standard Deviation 2.07 |
| Placebo | 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 | Mean IgM at baseline (mcg/mL) | 3.0 mcg/mL | Standard Deviation 2.8 |
| Placebo | 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 | Mean IgM change from baseline (mcg/mL) | 0.57 mcg/mL | Standard Deviation 0.83 |
Primary
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.
Time frame: Month 6 prevaccination (baseline) and Month 7 postvaccination
Population: Six subjects from the LAD-treated arm and 5 subjects from the placebo-treated arm were assessed for interferon gamma. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Mean interferon gamma at baseline | 0.2 spots/1 million cells | Standard Deviation 3.2 |
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Mean interferon gamma change from baseline | 2.09 spots/1 million cells | Standard Deviation 4.85 |
| Placebo | 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 | Mean interferon gamma at baseline | -1.4 spots/1 million cells | Standard Deviation 3.2 |
| Placebo | 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 | Mean interferon gamma change from baseline | 10.25 spots/1 million cells | Standard Deviation 11.41 |
Secondary
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.
Time frame: Pretransplant and posttransplant (Month 12)
Population: Nine subjects from the LAD-treated arm and 7 subjects from the placebo-treated arm were assessed for TREC per 100,000 CD4+ cells. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Baseline TREC per 100,000 CD4+ cells | 67.524 TREC /100,000 CD4+ cells | Standard Deviation 47.0863 |
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Mean change in TREC from baseline to final visit | 522.321 TREC /100,000 CD4+ cells | Standard Deviation 920.79 |
| Placebo | 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 | Baseline TREC per 100,000 CD4+ cells | 173.712 TREC /100,000 CD4+ cells | Standard Deviation 206.1733 |
| Placebo | 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 | Mean change in TREC from baseline to final visit | -63.950 TREC /100,000 CD4+ cells | Standard Deviation 235.561 |
Comparison: The final on treatment values were included in the analysis.p-value: 0.125ANOVA
Secondary
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.
Time frame: Pretransplant and posttransplant (Month 12)
Population: Eight subjects from the LAD-treated arm and 5 subjects from the placebo-treated arm were assessed for TREC per 100,000 CD8+ cells. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Baseline mean for TREC per 100,000 CD8+ cells | 181.673 TREC /100,000 CD8+ cells | Standard Deviation 209.7599 |
| Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month | 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 | Mean change in TREC from baseline to final visit | -10.811 TREC /100,000 CD8+ cells | Standard Deviation 343.061 |
| Placebo | 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 | Mean change in TREC from baseline to final visit | -184.084 TREC /100,000 CD8+ cells | Standard Deviation 282.405 |
| Placebo | 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 | Baseline mean for TREC per 100,000 CD8+ cells | 364.414 TREC /100,000 CD8+ cells | Standard Deviation 280.3465 |
Comparison: The final on treatment values were included in the analysis.p-value: 0.299ANOVA