Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer
CTLA-4 Blockade With MDX-010 to Induce Graft-Versus-Malignancy Effects Following Allogeneic Hematopoietic Stem Cell Transplantation
6 other identifiers
interventional
21
1 country
5
Brief Summary
This phase I trial is studying how well ipilimumab works after allogeneic stem cell transplant in treating patients with persistent or progressive cancer. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2003
CompletedFirst Submitted
Initial submission to the registry
May 6, 2003
CompletedFirst Posted
Study publicly available on registry
May 7, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2008
CompletedMarch 27, 2013
March 1, 2013
5 years
May 6, 2003
March 26, 2013
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of grade 3 and 4 acute GVHD based on NCI CTC
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
Post-infusion day 60
Autoimmune reaction defined as >= grade 3 dysfunction of a vital organ or the graft
Up to 5 years
Secondary Outcomes (5)
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)
Up to 5 years
Incidence of extensive stage chronic GVHD
Post-infusion day 360
Disease response
Up to day 360 post ipilimumab infusion
Disease-free survival
Up to day 360 following antibody infusion
Overall survival
Up to 360 days post-infusion
Study Arms (1)
Treatment (ipilmumab and donor lymphocyte infusion)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Diagnosis of persistent or progressive hematologic malignancy or solid tumor after allogeneic hematopoietic stem cell transplantation (AHSCT)
- Patients are eligible for study entry at any time between post-transplantation day 90 and 3 years after withdrawal of immunosuppressive therapy
- Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) that meets any of the following criteria: hematologic relapse by standard criteria, hematologic persistence evidenced by bone marrow blasts \> 10% after day 30 post-AHSCT
- Cytogenetic progression as evidenced by an increase in the percentage of Philadelphia chromosome (Ph)1-positive metaphases (or Ph1-positive cells by fluorescent in situ hybridization) from complete cytogenetic response (0% Ph1-positive cells) to partial response (1-34% Ph1-positive cells); PR to minor response (35-94% Ph1-positive cells); or MR to no response (95-100% Ph1-positive cells)
- Resistance to imatinib mesylate, defined as disease progression (hematologic, cytogenetic, or molecular) during OR failure to respond to (i.e., lack of complete hematologic response after 3 months, lack of partial cytogenetic response after 6 months, or lack of complete cytogenetic response after 12 months) prior imatinib mesylate therapy
- Myelodysplastic syndromes that meet any of the following criteria:
- Hematologic relapse by standard criteria, cytogenetic relapse evidenced by recurrence of clonal abnormality in patients who achieved CCR after AHSCT, hematologic persistence evidenced by cytopenias not attributable to other post-transplant causes accompanied by characteristic morphological changes more than 90 days after AHSCT
- OR; Hematologic persistence evidenced by cytopenias not attributable to other post-transplant causes accompanied by characteristic morphological changes more than 90 days after AHSCT, or cytogenetic persistence evidenced by persistence of clonal abnormality more than 90 days after AHSCT
- Chronic lymphocytic leukemia that meets any of the following criteria:
- greater than 25% increase in absolute lymphocytosis of \> 5,000/mm3, greater than 25% increase in measurable lymphadenopathy, persistence of absolute lymphocytosis of \> 5,000/mm3 at day 90 or later after AHSCT, persistence of lymphadenopathy of ≥ 3 cm in diameter at day 90 or later after AHSCT
- Aggressive non-Hodgkin's lymphoma (e.g., diffuse large cell lymphoma, lymphoblastic lymphoma, mantle cell lymphoma, or peripheral T cell lymphoma), Hodgkin's lymphoma, OR solid tumor that meets any of the following criteria: greater than 50% increase in measurable or evaluable disease, persistence of measurable lesions \> 3.0 cm in diameter at day 90 or later after AHSCT OR;
- Persistence of malignancy by biopsy or positron emission tomography scan unless there is clear evidence of progression
- Multiple myeloma with demonstrated resistance to or intolerance of prior thalidomide and bortezomib unless these agents are contraindicated (e.g., due to peripheral neuropathy) and meeting any of the following criteria: greater than 25% increase in paraprotein band, abnormal quantitative immunoglobulin level, or urine protein excretion OR
- Greater than 25% increase in percent of plasma cells in the bone marrow (if \> 15%), presence of new lytic bone lesions, new extramedullary lesions OR ≥ 25% enlargement of existing extramedullary lesions, persistence of paraprotein band, abnormally elevated quantitative immunoglobulin level, or bone marrow plasmacytosis \> 15% for a period of at least 90 days after AHSCT
- At least 1 bidimensionally measurable lesion ≥ 1.5 cm in diameter
- +23 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Scripps Clinic - La Jolla
La Jolla, California, 92037, United States
University of California San Diego
La Jolla, California, 92093-0960, United States
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342, United States
Northside Hospital
Atlanta, Georgia, 30342, United States
Dana-Farber Harvard Cancer Center
Boston, Massachusetts, 02115, United States
Related Publications (1)
Bashey A, Medina B, Corringham S, Pasek M, Carrier E, Vrooman L, Lowy I, Solomon SR, Morris LE, Holland HK, Mason JR, Alyea EP, Soiffer RJ, Ball ED. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood. 2009 Feb 12;113(7):1581-8. doi: 10.1182/blood-2008-07-168468. Epub 2008 Oct 30.
PMID: 18974373DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ewa Carrier
University of California, San Diego
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 6, 2003
First Posted
May 7, 2003
Study Start
April 1, 2003
Primary Completion
April 1, 2008
Last Updated
March 27, 2013
Record last verified: 2013-03