Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer
|ClinicalTrials.gov Identifier: NCT00060372|
Recruitment Status : Completed
First Posted : May 7, 2003
Last Update Posted : March 27, 2013
|Condition or disease||Intervention/treatment||Phase|
|Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Childhood Myelodysplastic Syndromes Chronic Myelogenous Leukemia, BCR-ABL1 Positive Disseminated Neuroblastoma Malignant Neoplasm Ovarian Choriocarcinoma Ovarian Embryonal Carcinoma Ovarian Immature Teratoma Ovarian Mature Teratoma Ovarian Mixed Germ Cell Tumor Ovarian Monodermal and Highly Specialized Teratoma Ovarian Polyembryoma Ovarian Yolk Sac Tumor Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Malignant Testicular Germ Cell Tumor Recurrent Mantle Cell Lymphoma Recurrent Neuroblastoma Recurrent Ovarian Epithelial Cancer Recurrent Ovarian Germ Cell Tumor Refractory Chronic Lymphocytic Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Stage I Multiple Myeloma Stage II Multiple Myeloma Stage II Ovarian Epithelial Cancer Stage III Malignant Testicular Germ Cell Tumor Stage III Multiple Myeloma Stage III Ovarian Epithelial Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer Stage IV Ovarian Epithelial Cancer Testicular Choriocarcinoma Testicular Choriocarcinoma and Embryonal Carcinoma Testicular Choriocarcinoma and Seminoma Testicular Choriocarcinoma and Teratoma Testicular Choriocarcinoma and Yolk Sac Tumor Testicular Embryonal Carcinoma Testicular Embryonal Carcinoma and Seminoma Testicular Embryonal Carcinoma and Teratoma Testicular Embryonal Carcinoma and Teratoma With Seminoma Testicular Embryonal Carcinoma and Yolk Sac Tumor Testicular Embryonal Carcinoma and Yolk Sac Tumor With Seminoma Testicular Teratoma Testicular Yolk Sac Tumor Testicular Yolk Sac Tumor and Teratoma Testicular Yolk Sac Tumor and Teratoma With Seminoma||Drug: ipilimumab Drug: therapeutic allogeneic lymphocytes||Phase 1|
I. To determine the dose of MDX-010 (ipilimumab) that can safely be administered to patients with persistent or progressive malignancy following allo-HCT.
II. To determine the pharmacokinetics of different doses of MDX-010 administered as a single dose to patients with persistent or progressive malignancy following allo-HCT.
III. By assessment of aims 1 and 2, to determine the best dosing regimen for further study of CTLA-4 blockade in conjunction with escalating dose donor-leukocyte infusions (DLI) in patients with evidence of residual or progressive malignancy following allo-HCT.
IV. To assess if there is preliminary evidence of efficacy following the administration of MDX-010 in this population.
Patients receive ipilimumab intravenously (IV) over 90 minutes.
Cohorts of 3-6 patients receive escalating doses of ipilimumab until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients with persistent or progressive disease at 60 days after ipilimumab administration and no evidence of graft-versus-host disease receive donor lymphocyte infusions every 60 days for a total of 3 infusions.
Patients are followed at 4, 5, 6, 9, and 12 months and then annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||CTLA-4 Blockade With MDX-010 to Induce Graft-Versus-Malignancy Effects Following Allogeneic Hematopoietic Stem Cell Transplantation|
|Study Start Date :||April 2003|
|Primary Completion Date :||April 2008|
Experimental: Treatment (ipilmumab and donor lymphocyte infusion)
Patients receive ipilimumab IV over 90 minutes. Cohorts of 3-6 patients receive escalating doses of ipilimumab until the MTD is determined. The MTD is the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients with persistent or progressive disease at 60 days after ipilimumab administration and no evidence of graft-versus-host disease receive donor lymphocyte infusions every 60 days for a total of 3 infusions.
Other Names:Drug: therapeutic allogeneic lymphocytes
Other Name: ALLOLYMPH
- Incidence of grade 3 and 4 acute GVHD based on NCI CTC [ Time Frame: 60 days following administration of ipilimumab ]
- Incidence of graft rejection following ipilimumab defined as the percentage of patients entered who demonstrate =< 10% donor T-cell chimerism [ Time Frame: Post-infusion day 60 ]
- Autoimmune reaction defined as >= grade 3 dysfunction of a vital organ or the graft [ Time Frame: Up to 5 years ]
- Polyclonal T-cell activation monitored by clinical assessment and laboratory evidence (anti CD3, CD4, CD8) and markers of activation (anti CD69, CD25, CD44 and MHC class II) [ Time Frame: Up to 5 years ]
- Incidence of extensive stage chronic GVHD [ Time Frame: Post-infusion day 360 ]
- Disease response [ Time Frame: Up to day 360 post ipilimumab infusion ]
- Disease-free survival [ Time Frame: Up to day 360 following antibody infusion ]Kaplan- Meier estimates of probability will be used.
- Overall survival [ Time Frame: Up to 360 days post-infusion ]Kaplan- Meier estimates of probability will be used.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00060372
|United States, California|
|Scripps Clinic - La Jolla|
|La Jolla, California, United States, 92037|
|University of California San Diego|
|La Jolla, California, United States, 92093-0960|
|United States, Georgia|
|Blood and Marrow Transplant Group of Georgia|
|Atlanta, Georgia, United States, 30342|
|Atlanta, Georgia, United States, 30342|
|United States, Massachusetts|
|Dana-Farber Harvard Cancer Center|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Ewa Carrier||University of California, San Diego|