Common use of Clinical Trial Clause in Contracts

Clinical Trial. Based on the findings of this preclinical study, the NCI sponsored a Phase 2 clinical study to evaluate the ability of this new idiotype vaccine to elicit tumor-specific T-cell immunity, as measured by the ability of patient T cells to specifically lyse their own tumor cells in vitro, and to exert antitumor effects as measured by the elimination of t(14;18)-bearing cells from the peripheral blood of uniformly treated FL patients in first CR (complete remission). Patients in this study were previously untreated and received a uniform chemotherapy regimen, PACE; Prednisone, Adriamycin, Cytoxan, and Etoposide. (modified ProMACE without methotrexate). By design, therefore, they comprised a very homogeneous patient population in a minimal residual disease state. Of 35 patients, 23 (66%) achieved CR by standard clinical criteria. One of the patients was lost to analysis because of early relapse within six months, and two were excluded because a vaccine could not be made. This left a total study group of 20 patients in CR. Six to 15 months after completion of chemotherapy, these 20 patients were treated with a series of five monthly vaccinations with autologous FL Ig protein (0.5 mg) conjugated to KLH, together with local granulocyte-macrophage colony-stimulating factor (GM-CSF, 100 or 500 mcg/m2) subcutaneously (19). Eighteen of 20 patients remain in continuous, first complete remission (median: 42+ months from completion of chemotherapy, range: 28+ to 53+). UPN 9 and 14 relapsed at 15 and 7 months after completion of vaccine therapy, respectively. UPN 9 had never cleared the t(14;18)-bearing cells from the peripheral blood; UPN 14 did not have the MBR rearrangement and thus, molecular CR status could not be established. The rationale for a pivotal, randomized trial, which is the subject of this CRADA is thus based on three independent results from this completed Phase 2 study: (1) tumor-specific CD8+ T-cell responses (cytotoxicity against autologous FL targets and cytokine production) were seen in 17 of 20 (85%) vaccinated patients, (2) 8 of 11 (73%) patients sampled after completion of vaccination converted to PCR negative and have maintained both PCR negativity and clinical CR, and (3) with a median follow-up of 36+ months after completion of chemotherapy (range 22+ to 47+ months), 18 of 20 (90%) patients remain in continuous clinical CR. Taken together, these data suggest that idiotype vaccination can elicit a tumor-specific response that is associated with clearance of residual tumor cells from the blood in the majority of patients with FL. It remains to be determined whether molecular CR is associated with prolonged disease-free survival. However, this systematic analysis of molecular response rate provides the first evidence for an anti-tumor effect of vaccination. Finally, this study established GM-CSF as an essential component of the vaccine strategy, particularly for induction of CD8+ T-cell responses.

Clinical Trial. Based on the findings of this preclinical study, the NCI sponsored a Phase 2 clinical study to evaluate the ability of this new idiotype vaccine to elicit tumor-specific T-cell immunity, as measured by the ability of patient T cells to specifically lyse their own tumor cells in vitro, and to exert antitumor effects as measured by the elimination of t(14;18)-bearing t(14; 18)-bearing cells from the peripheral blood of uniformly treated FL patients in first CR (complete remission). Patients in this study were previously untreated and received a uniform chemotherapy regimen, PACE; Prednisone, Adriamycin, Cytoxan, and Etoposide. (modified ProMACE without methotrexate). By design, therefore, they comprised a very homogeneous patient population in a minimal residual disease state. Of 35 patients, 23 (66%) achieved CR by standard clinical criteria. One of the patients was lost to analysis because of early relapse within six months, and two were excluded because a vaccine could not be made. This left a total study group of 20 patients in CR. Six to 15 months after completion of chemotherapy, these 20 patients were treated with a series of five monthly vaccinations with autologous FL Ig protein (0.5 mg) conjugated to KLH, together with local granulocyte-macrophage colony-stimulating factor (GM-CSF, 100 or 500 mcg/m2) subcutaneously (19). Eighteen of 20 patients remain in continuous, first complete remission (median: 42+ months from completion of chemotherapy, range: 28+ to 53+). UPN 9 and 14 relapsed at 15 and 7 months after completion of vaccine therapy, respectively. UPN 9 had never cleared the t(14;18)-bearing t(14; 18)-bearing cells from the peripheral blood; UPN 14 did not have the MBR rearrangement and thus, molecular CR status could not be established. The rationale for a pivotal, randomized trial, which is the subject of this CRADA is thus based on three independent results from this completed Phase 2 study: (1) tumor-specific CD8+ T-cell responses (cytotoxicity against autologous FL targets and cytokine production) were seen in 17 of 20 (85%) vaccinated patients, (2) 8 of 11 (73%) patients sampled after completion of vaccination converted to PCR negative and have maintained both PCR negativity and clinical CR, and (3) with a median follow-up of 36+ months after completion of chemotherapy (range 22+ to 47+ months), 18 of 20 (90%) patients remain in continuous clinical CR. Taken together, these data suggest that idiotype vaccination can elicit a tumor-specific response that is associated with clearance of residual tumor cells from the blood in the majority of patients with FL. It remains to be determined whether molecular CR is associated with prolonged disease-free survival. However, this systematic analysis of molecular response rate provides the first evidence for an anti-tumor effect of vaccination. Finally, this study established GM-CSF as an essential component of the vaccine strategy, particularly for induction of CD8+ T-cell responses.

Clinical Trial. Based on the findings of this preclinical study, the NCI sponsored a Phase 2 clinical study to evaluate the ability of this new idiotype vaccine to elicit tumor-specific T-cell immunity, as measured by the ability of patient T cells to specifically lyse their own tumor cells in vitro, and to exert antitumor effects as measured by the elimination of t(14;18)-bearing t(l4;18)-bearing cells from the peripheral blood of uniformly treated FL patients in first CR (complete remission). Patients in this study were previously untreated and received a uniform chemotherapy regimen, PACE; Prednisone, Adriamycin, Cytoxan, and Etoposide. (modified ProMACE without methotrexate). By design, therefore, . they comprised a very homogeneous patient population in a minimal residual disease state. Of 35 patients, 23 (66%) achieved CR by standard clinical criteria. One of the patients was lost to analysis because of early relapse within six months, and two were excluded because a vaccine could not be made. This left a total study group of 20 patients in CR. Six to 15 months after completion of chemotherapy, these 20 patients were treated with a series of five monthly vaccinations with autologous FL Ig protein (0.5 mg) conjugated to KLH, together with local granulocyte-macrophage colony-stimulating factor (GM-CSF, 100 or 500 mcg/m2) subcutaneously (19). Eighteen of 20 patients remain in continuous, first complete remission (median: 42+ months from completion of chemotherapy, range: 28284+ to 53+). UPN 9 and 14 relapsed at 15 and 7 months after completion of vaccine therapy, respectively. UPN 9 had never cleared the t(14;18)-bearing cells from the peripheral blood; UPN 14 did not have the MBR rearrangement and thus, molecular CR status could not be established. The rationale for a pivotal, randomized trial, which is the subject of this CRADA is thus based on three independent results from this completed Phase 2 study: (1I) tumor-specific CD8+ T-cell responses (cytotoxicity against autologous FL targets and cytokine production) were seen in 17 of 20 (85%) vaccinated patients, (2) 8 of 11 1 1 (73%) patients sampled after completion of vaccination converted to PCR negative and have maintained both PCR negativity and clinical CR, and (3) with a median follow-up of 36+ months after completion of chemotherapy (range 22+ to 47+ months), 18 of 20 (90%) patients remain in continuous clinical CR. Taken together, these data suggest that idiotype vaccination can elicit a tumor-specific response that is associated with clearance of residual tumor cells from the blood in the majority of patients with FL. It remains to be determined whether molecular CR is associated with prolonged disease-free survival. However, this systematic analysis of molecular response rate provides the first evidence for an anti-tumor effect of vaccination. Finally, this study established GM-CSF as an essential component of the vaccine strategy, particularly for induction of CD8+ T-cell responses.. NCI CRADA 01030