Bone Marrow Transplant clinical trials at University of California Health

Patients in need of an allogeneic hematopoietic cell transplant (HCT) are at risk of developing graft-versus-host-disease (GVHD). In certain clinical situations, the optimal approach to minimize the risk of GVHD is to perform ex vivo alpha-beta T-cell depletion of the donor cells. However, the CliniMACS® Device is FDA-approved only for a narrow indication. All other uses of ex vivo processed cells must be done under a feasibility study protocol.

This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose chemotherapy followed by conventional RT in patients who did not respond to induction chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to chemotherapy before receiving radiation therapy, are more likely to be free of the disease for a longer time than are patients for whom the chemotherapy does not efficiently eliminate or reduce the size of the tumor. The purpose of this study is to see how well the tumors respond to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dose chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving treatment based on the response to induction chemotherapy may lower the side effects of radiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT.

The researchers are doing this study to find out whether emapalumab or a combination of fludarabine and dexamethasone are effective in preparing people with a primary immune regulatory disorder (PIRD) and/or an autoinflammatory condition to receive a stem cell transplant. The researchers will look at how well the study treatments reduce inflammation and aid in the engraftment process (the process of donated stem cells traveling to the bone marrow, where they begin to make new immune cells. "Funding Source - FDA OOPD"

Patients are in 2 cohorts: Cohort 1: dexamethasone, methotrexate, ifosfamide, pegaspargase, and etoposide (modified SMILE) chemotherapy regimen alone and pembrolizumab in children, adolescents, and young adults with advanced stage NK lymphoma and leukemia Cohort 2: combining pralatrexate (PRX) (Cycles 1, 2, 4, 6) and brentuximab vedotin (BV) (Cycles 3, 5) to cyclophosphamide, doxorubicin, and prednisone in children, adolescent, and young adults with advanced peripheral T-cell lymphoma (non-anaplastic large cell lymphoma or non-NK lymphoma/leukemia) . Both groups proceed to allogeneic stem cell transplant with disease response.

This study will validate a previously developed pediatric prognostic biomarker algorithm aimed at improving prediction of risk for the later development of chronic graft-versus-host disease (cGvHD) in children and young adults undergoing allogeneic hematopoietic stem cell transplant. By developing an early risk stratification of patients into low-, intermediate-, and high-risk for future cGvHD development (based upon their biomarker profile, before the onset of cGvHD), pre-emptive therapies aimed at preventing the onset of cGvHD can be developed based upon an individual's biological risk profile. This study will also continue research into diagnostic biomarkers of cGvHD, and begin work into biomarker models that predict clinical response to cGvHD therapies.

Hematopoietic stem cell transplant (HSCT) is an effective but toxic therapy and pulmonary morbidity affects as many as 25% of children receiving transplant. Early pulmonary injury includes diffuse alveolar hemorrhage (DAH), thrombotic microangiopathy (TMA) interstitial pneumonitis (IPS) and infection, while later, bronchiolitis obliterans is a complication of chronic GVHD associated with severe morbidity and mortality. Improved diagnosis and treatment of pulmonary complications are urgently needed as survival after HSCT improves, and as HSCT is increasingly used for non-malignant disorders such as sickle cell disease. Currently, there are large and important gaps in the investigator's knowledge regarding incidence, etiology and optimal treatment of pulmonary complications. Moreover, young children unable to perform spirometry are often diagnosed late, and strategies for monitoring therapeutic response are limited. This is a prospective multi-institutional cohort study in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Assembly of a large prospective uniformly screened cohort of children receiving HSCT, together with collection of biological samples, will be an effective strategy to identify mechanisms of lung injury, test novel diagnostic strategies for earlier diagnosis, and novel treatments to reduce morbidity and mortality from lung injury after transplant.