Ignite Creation Date:
2024-05-05 @ 6:31 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00499577
Status:
COMPLETED
Last Update Posted:
2014-01-10
First Post:
2007-07-10
Brief Title:
Stem Cell Transplant Chemotherapy and Biological Therapy in Treating Patients With High-Risk or Refractory Multiple Myeloma
Sponsor:
University of Maryland Greenebaum Cancer Center
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase III Combination Immunotherapy After ASCT for Advanced Myeloma to Study HTERT Vaccination Followed by Adoptive Transfer of Vaccine-Primed Autologous T Cells
Status:
COMPLETED
Status Verified Date:
2009-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Vaccines made from peptides may help the body build an effective immune response to kill tumor cells Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer A stem cell transplant using stem cells from the patient may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells Giving an infusion of the donors T cells after the transplant may help destroy any remaining cancer cells
PURPOSE This phase III trial is studying the side effects of stem cell transplant given together with chemotherapy and biological therapy and to see how well it works in treating patients with high-risk or refractory multiple myeloma
PURPOSE This phase III trial is studying the side effects of stem cell transplant given together with chemotherapy and biological therapy and to see how well it works in treating patients with high-risk or refractory multiple myeloma
Detailed Description:
OBJECTIVES
Primary
To evaluate the safety of combination immunotherapy using activated T-cells and an hTERTsurvivin multipeptide vaccine in the post-autotransplant autologous stem cell transplantation setting and whether it delays hematopoietic recovery or induces autoimmune events
To determine whether the strategy of infusing vaccine-primed T-cells early after transplant in conjunction with post-transplant booster immunizations leads to the induction of cellular immune responses to the putative tumor antigens hTERT the catalytic subunit of telomerase and survivin
To determine if combination immunotherapy as delivered to arm I patients increases the frequency of delayed paraprotein responses between 60 days and 6 months post-transplant sufficient to upgrade the maximal level of myeloma response when compared to non-vaccinated arm II patients
Secondary
To determine if adoptive transfer of hTERTsurvivin-primed T-cells in conjunction with multi-peptide booster immunizations generates cytotoxic T-cell responses to autologous myeloma cells in vivo
To evaluate myeloma clinical responses including the frequency of complete and partial responses and the 1 2-year event-free and overall survivals
To measure antibody responses to 4 of the 7 serotypes contained in the pneumococcal polyvalent vaccine as well as T-cell responses to the CRM-197 carrier protein and to a CMV peptide antigen
To evaluate levels of hTERT and survivin expression in patient myeloma cells
OUTLINE This is a multicenter study Patients are stratified according to HLA-A2 status positive vs negative Patients are assigned to 1 of 2 treatment groups based on stratification
Immunization 1
Group 1 HLA-A2 positive Patients receive the following peptides emulsified in incomplete Freunds adjuvant VG I hTERT I540 peptide ii hTERT R572Y peptide iii hTERT D988Y peptide iv survivin Sur1M2 peptide and v CMV control peptide N495 subcutaneously SC Patients also receive sargramostim GM-CSF SC and pneumococcal conjugate vaccine PCV intramuscularly IM
Group 2 Patients receive PCV vaccine IM and GM-CSF SC
Steady-state T-cell harvestingAbout 10 days range 7-14 after immunization 1 all patients undergo a mononuclear cell apheresis procedure to collect steady-state T-cells that are cryopreserved for later expansion
Stem cell mobilization After completion of the mononuclear cell apheresis procedure all patients are offered DT-PACE chemotherapy for cytoreduction and stem cell mobilization This regimen is as follows dexamethasone once daily for 4 days thalidomide once daily for 4 days cisplatin IV continuously over 4 days patients with serum creatinine levels 20 mgdL do not receive cisplatin doxorubicin hydrochloride IV continuously over 4 days cyclophosphamide IV continuously over 4 days etoposide IV continuously over 4 days Patients also receive filgrastim G-CSF SC once daily starting on the day after completion of chemotherapy An acceptable alternative for stem cell mobilization is to use cyclophosphamide IV over 12 hours or for patients who require that outpatient stem cell mobilization procedures be performed cyclophosphamide IV over 2 hours The cyclophosphamide mobilization regimen should be used if the patient has already received DTPACE as part of the pre-transplant therapy
High-dose therapy High-dose therapy will consist of melphalan IV over 20 minutes on day -1 Autologous stem cell infusion takes place on day 0 at least 18 hours after the administration of the high-dose melphalan Stem cells are infused IV over 20-60 minutes G-CSF SC should be administered beginning on day 5
Autologous T-cell expansion and infusion Cryopreserved cells are expanded ex vivo for up to 12 days and prepared for infusion on day 2 post-transplant
Infusion of autologous T-cells The costimulated activated T-cells are infused over 20-60 minutes on day 2 of transplant
Immunizations 2 3 and 4
Group 1 On days 14 42 and 90 post-transplant patients receive peptides PCV and GM-CSF as in group I of immunization 1
Group 2 On day 14 42 90 post-transplant patients receive PCV and GM-CSF as in group II of immunization 1
Maintenance therapy At day 180 post-transplant after completion of post-transplant immunological assessments patients receive low-dose thalidomide in the absence of disease progression or unacceptable toxicity
Blood is collected at T-cell harvest and days 14 60 100 and 180 post-transplant Samples are analyzed by quantitative CD3CD4CD8 studies cellular immunoassays antibody immunoassays and gene expression
After completion of study treatment patients are followed periodically
Primary
To evaluate the safety of combination immunotherapy using activated T-cells and an hTERTsurvivin multipeptide vaccine in the post-autotransplant autologous stem cell transplantation setting and whether it delays hematopoietic recovery or induces autoimmune events
To determine whether the strategy of infusing vaccine-primed T-cells early after transplant in conjunction with post-transplant booster immunizations leads to the induction of cellular immune responses to the putative tumor antigens hTERT the catalytic subunit of telomerase and survivin
To determine if combination immunotherapy as delivered to arm I patients increases the frequency of delayed paraprotein responses between 60 days and 6 months post-transplant sufficient to upgrade the maximal level of myeloma response when compared to non-vaccinated arm II patients
Secondary
To determine if adoptive transfer of hTERTsurvivin-primed T-cells in conjunction with multi-peptide booster immunizations generates cytotoxic T-cell responses to autologous myeloma cells in vivo
To evaluate myeloma clinical responses including the frequency of complete and partial responses and the 1 2-year event-free and overall survivals
To measure antibody responses to 4 of the 7 serotypes contained in the pneumococcal polyvalent vaccine as well as T-cell responses to the CRM-197 carrier protein and to a CMV peptide antigen
To evaluate levels of hTERT and survivin expression in patient myeloma cells
OUTLINE This is a multicenter study Patients are stratified according to HLA-A2 status positive vs negative Patients are assigned to 1 of 2 treatment groups based on stratification
Immunization 1
Group 1 HLA-A2 positive Patients receive the following peptides emulsified in incomplete Freunds adjuvant VG I hTERT I540 peptide ii hTERT R572Y peptide iii hTERT D988Y peptide iv survivin Sur1M2 peptide and v CMV control peptide N495 subcutaneously SC Patients also receive sargramostim GM-CSF SC and pneumococcal conjugate vaccine PCV intramuscularly IM
Group 2 Patients receive PCV vaccine IM and GM-CSF SC
Steady-state T-cell harvestingAbout 10 days range 7-14 after immunization 1 all patients undergo a mononuclear cell apheresis procedure to collect steady-state T-cells that are cryopreserved for later expansion
Stem cell mobilization After completion of the mononuclear cell apheresis procedure all patients are offered DT-PACE chemotherapy for cytoreduction and stem cell mobilization This regimen is as follows dexamethasone once daily for 4 days thalidomide once daily for 4 days cisplatin IV continuously over 4 days patients with serum creatinine levels 20 mgdL do not receive cisplatin doxorubicin hydrochloride IV continuously over 4 days cyclophosphamide IV continuously over 4 days etoposide IV continuously over 4 days Patients also receive filgrastim G-CSF SC once daily starting on the day after completion of chemotherapy An acceptable alternative for stem cell mobilization is to use cyclophosphamide IV over 12 hours or for patients who require that outpatient stem cell mobilization procedures be performed cyclophosphamide IV over 2 hours The cyclophosphamide mobilization regimen should be used if the patient has already received DTPACE as part of the pre-transplant therapy
High-dose therapy High-dose therapy will consist of melphalan IV over 20 minutes on day -1 Autologous stem cell infusion takes place on day 0 at least 18 hours after the administration of the high-dose melphalan Stem cells are infused IV over 20-60 minutes G-CSF SC should be administered beginning on day 5
Autologous T-cell expansion and infusion Cryopreserved cells are expanded ex vivo for up to 12 days and prepared for infusion on day 2 post-transplant
Infusion of autologous T-cells The costimulated activated T-cells are infused over 20-60 minutes on day 2 of transplant
Immunizations 2 3 and 4
Group 1 On days 14 42 and 90 post-transplant patients receive peptides PCV and GM-CSF as in group I of immunization 1
Group 2 On day 14 42 90 post-transplant patients receive PCV and GM-CSF as in group II of immunization 1
Maintenance therapy At day 180 post-transplant after completion of post-transplant immunological assessments patients receive low-dose thalidomide in the absence of disease progression or unacceptable toxicity
Blood is collected at T-cell harvest and days 14 60 100 and 180 post-transplant Samples are analyzed by quantitative CD3CD4CD8 studies cellular immunoassays antibody immunoassays and gene expression
After completion of study treatment patients are followed periodically
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MSGCC-0610-GCC | None | None | None |
| UPCC-0610-GCC | None | None | None |