Madison, Wisconsin 53705


Purpose:

This phase I trial studies the safety of transplantation with a haploidentical donor peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with the immunomodulating drug, Zoledronate, given in the post-transplant period to treat pediatric patients with relapsed or refractory hematologic malignancies or high risk solid tumors.


Study summary:

REDUCED-INTENSITY CONDITIONING REGIMEN: Patients receive anti-thymocyte globulin (ATG) intravenously (IV) on days -12 to -9, fludarabine phosphate IV on days -8 to -5, thiotepa IV twice daily (BID) on day -4, and melphalan IV on days -3 to -2. PERIPHERAL BLOOD STEM CELL TRANSPLANTATION: Patients undergo TCR-αβ+ and CD19+ depleted haploidentical donor peripheral blood stem cell transplantation on day 0. ZOLEDRONATE ADMINISTRATION: Patients receive zoledronate IV after transplant as determined by their assigned treatment group (Cohort). Patients in Cohort A do not receive zoledronate. Follow-up assessments will occur after transplantation.


Criteria:

Inclusion Criteria: Availability of an eligible haploidentical donor Hematologic malignancy Patients with hematologic malignancy must have no HLA identical sibling or suitable unrelated donor OR time needed to find an acceptable unrelated donor match would likely result in disease progression such that the patient may become ineligible for any type of potentially curative transplant - Relapsed or primary therapy-refractory AML with bone marrow blast < 20% - High-risk refractory or relapsed ALL in patients for whom transplantation is deemed indicated (primary induction failure or hypodiploidy, relapse occurring < 30 months from diagnosis, relapse after previous allogeneic hematopoietic stem cell transplant [allo-HSCT], relapse after 2nd remission) - Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem cell transplant (auto-HSCT) - Hodgkin lymphoma relapsing after auto-HSCT - Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd remission or VGPR and therefore ineligible to receive auto-HSCT - Non-Hodgkin lymphoma relapsing after auto-HSCT - Myelodysplastic Syndrome/Myeloproliferative Syndrome Solid Tumor Patients with solid tumor must have failed or have been ineligible to receive auto-HSCT or if auto-HSCT would not offer > 20% chance of cure - Neuroblastoma - high risk with relapsed or refractory disease - Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor or other high-risk extracranial solid tumors) - Relapsed or primary refractory metastatic - 1st complete remission, but very high-risk features (i.e., < 20% survival with conventional therapy) - Osteosarcoma - Failure to achieve Complete Response (CR) following initial therapy - Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery and/or chemotherapy Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance score of ≥ 60 Life expectancy of ≥ 3 months Patient must have fully recovered from acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study Study enrollment no earlier than 3 months after preceding HSCT Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2 Total bilirubin < 3 mg/dL ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram No evidence of dyspnea at rest No supplemental oxygen requirement If measured, carbon monoxide diffusion capacity (DLCO) >50% No severe peripheral neuropathy, signs of leukoencephalopathy or active Central Nervous System (CNS) infection Patients with seizure disorders may be enrolled if seizures are well controlled on anticonvulsant therapy If of reproductive potential, negative pregnancy test and willing to use effective birth control method Informed consent from patient or legal guardian (if patient is minor) Exclusion Criteria: Pregnant or breast-feeding HIV infection Heart failure or uncontrolled cardiac rhythm disturbance Active infection Prior organ allograft Significant serious intercurrent illness unrelated to cancer or its treatment not covered by other exclusion criteria expected to significantly increase the risk of HSCT Any mental or physical condition, in the opinion of the PI (or PI designee), which could interfere with the ability of the subject (or the only parent or legal guardian available to care for the subject) to understand or adhere to the requirements of the study Enrollment in any other clinical study from screening up to Day 100 (unless PI judges such enrollment would not interfere with endpoints of this study)


NCT ID:

NCT02508038


Primary Contact:

Principal Investigator
Mario Otto, MD, PhD
University of Wisconsin, Madison

Jenny Weiland
Phone: 608-890-8070
Email: PedsHemOncResearch@lists.wisc.edu


Backup Contact:

Celeste Matsushima
Phone: 608-890-8069


Location Contact:

Madison, Wisconsin 53705
United States

Pediatric HemOnc Main Line
Phone: 608-263-6200
Email: PEDSHemOncResearch@lists.wisc.edu

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 22, 2017

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


Click to view Full Listing

If you would like to be contacted by the clinical trial representative please fill out the form below.