A Phase II Trial of Reduced Intensity Conditioning and Haploidentical BMT for High-risk Solid Tumors
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|ClinicalTrials.gov Identifier: NCT01804634|
Recruitment Status : Recruiting
First Posted : March 5, 2013
Last Update Posted : June 17, 2016
|Condition or disease||Intervention/treatment||Phase|
|Refractory and/or Relapsed Metastatic Solid Tumors||Drug: Cyclophosphamide Drug: Fludarabine Radiation: low dose total body irradiation Drug: Melphalan Drug: Sirolimus||Phase 2|
Allogeneic hematopoietic stem cell transplantation (HSCT) may be associated with a clinically significant "graft-versus-tumor" (GVT) effect, even against disease that is unresponsive to chemotherapy and radiation therapy. Graft-vs.-tumor (GVT) effects have been described after allogeneic HCT for neuroblastoma, Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, melanoma and hepatoblastoma.
Our goal is to maximize a T cell and NK cell mediated graft versus tumor effect in poor prognosis solid tumor patients using haploidentical donors, T cell replete bone marrow, and a unique post-transplant immunosuppression regimen containing post transplantation Cy and an mTOR inhibitor. This therapy will be widely applicable because almost all patients have a half-matched donor available (parent or sibling). We hope to demonstrate the safety and feasibility of this therapy in anticipation of combining this platform with additional post-transplantation therapy such as cryoablation, Donor Lymphocyte Infusion (DLI), stem cell directed therapy, immunologic checkpoint inhibitors, and/or metabolic inhibitors.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Reduced Intensity Conditioning and Partially HLA-mismatched (HLA-haploidentical) Bone Marrow Transplantation for High-risk Solid Tumors|
|Study Start Date :||February 2013|
|Estimated Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||December 2018|
Experimental: Reducued intesity conditioning
Given our promising results with low rates of GVHD and TRM using non-myeloablative haploidentical BMT in hematologic malignancies, we will use this backbone for very high risk solid tumors in order to maximize a graft versus tumor effect with allogeneic T cells and NK cells for patients with poor prognosis. We will modify our current regimen to include a reduced intensity dose of melphalan as an additional chemotherapeutic agent in the preparative regimen, as melphalan has commonly been incorporated into the myeloablative preparative regimens for solid tumors because of its tolerable side effect profile and anti-tumor efficacy.84 Sirolimus will be given post- transplant because of the potential for its additional anti-tumor benefit.
Other Name: cytoxanDrug: Fludarabine Radiation: low dose total body irradiation Drug: Melphalan Drug: Sirolimus
- Donor cell engraftment [ Time Frame: 14-60 Days ]To estimate the incidence of donor cell engraftment following reduced intensity conditioning, HLA-mismatched BMT for patients with high risk high-risk solid tumor malignancies.
- Overall survival [ Time Frame: 1-2 years ]To estimate overall survival in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.
- Relapse [ Time Frame: 1-2 years ]To estimate overall relapse, in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.
- Non-Relapse Mortality [ Time Frame: 1-2 years ]To estimate overall non-relapse mortality in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.
- Document toxicities [ Time Frame: 30-180 days ]To document rates of acute and chronic GVHD, unexpected toxicities after RIC haploidentical BMT.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01804634
|Contact: Heather Symons, MD, MHSemail@example.com|
|United States, Maryland|
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: Heather Symons, MD, MHS 410-502-4997 firstname.lastname@example.org|
|Principal Investigator: Heather Symons, MD, MHS|
|Principal Investigator:||Heather Symons, MD, MHS||Johns Hopkins University|