araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: A Clinical Research of CAR T Cells Targeting CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma

Summary: The main purpose of this research is to verify the safety of CD19 targeted chimeric antigen receptor T cells and to determine the proper dosage of CAR T cells infused.

Detailed description: Nowadays refractory or relapsed leukemia/lymphoma lacks effective treatment. Innovative therapy is urgently required. Chimeric antigen receptor (CAR)-modified T cells have demonstrated great successes in treating even late stage cluster of differentiation antigen 19 (CD19) positive B cell malignancies. To design better CAR T cells, we have developed new CD19 CARs. Preclinical studies have demonstrated effective killing of CD19 target cells. In this study, the CD19 CARs, will be evaluated in CD19 positive leukemia/lymphoma patients. The primary goal is to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, tumor targeting and disease status after treatment will also be evaluated.

Eligibility: Inclusion Criteria:
  1. Relapsed or refractory B cell derived acute lymphoblastic leukemia(ALL), chronic lymphocytic leukemia(CLL) and non-hodgkin lymphoma.
  2. KPS>60.
  3. Life expectancy>3 months.
  4. Gender unlimited, age from 12 years to 75 years.
  5. Disease progresses but reserves reaction to recent treatments.
  6. Patients who have failed at least one line of a standard treatment.
  7. No serious mental disorder.
  8. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate pulmonary function as indicated by room air oxygen saturation of >94%, and adequate renal function(Cr≤133umol/L).
  9. No other serious diseases(autoimmune disease, immunodeficiency etc.).
  10. No other tumors.
  11. Patients volunteer to participate in the research.
  Exclusion Criteria:
  1. HIV affected.
  2. Patients are allergic to cytokines.
  3. Central nervous system leukemia within 28 days.
  4. Uncontrolled active infection.
  5. Acute or chronic GVHD.
  6. Treated with T cell inhibitor.
  7. Pregnancy and nursing females.
  8. Other situations we think improper for the research.

Relevance to patient case: not relevant
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: The Effect of Deferasirox on Response Rate of Acute Leukemia Patients Not Treated by Standard Chemotherapy Regimens

Summary: The purpose of this study is to determine whether deferasirox is effective in the treatment of acute lymphatic leukemia (ALL) and acute Myeloid leukemia (AML).

Detailed description: Many studies have demonstrated that Iron is essential for the metabolism, cell cycle regulation and metastasis in different cancer cell lines. It is also believed that Iron concentration will increase in cancer cells by enhancing expression of TFR-1 receptors and in case of receptor saturation, non-receptor-mediated pinocytosis would be a significant pathway for more iron intake. Iron deficiency may lead to increase P 53 which consequently will stop cell mitosis in G1-S state. It also increases expression of N-myc down-regulated gene 1 which can suppress metastasis in cancer. It has been suggested that Iron chelators may decrease leukemic tumor growth in animal models of acute myeloid leukemia (AML). Some other case studies demonstrated the role of Iron chelators in relapse and/or refractory AML. Finally a phase 1 clinical study is undertaken for evaluate the role of Tiapine and cytarabine for adult AML and high-risk myelodysplastic syndrome. So in this study the investigators try to evaluate the role of iron chelating agent (deferasirox) for patients with acute lymphatic leukemia (ALL) and AML patients who cannot be treated with standard chemotherapy regimes .

Eligibility: Inclusion Criteria:
  1. Patients with acute leukemia (myeloid or lymphoblastic) who do not receive the standard chemotherapy regimens for treatment; because of the following reasons:
  1. age > 65
  2. existence of another illness, such as heart failure (EF> 40)
  2. Ferritin < 500 μg / l
  3. Not existence of other co morbidity
  4. GFR > 40
  Exclusion Criteria:
  1. GFR < 40
  2. Control group become iron overloaded (Ferritin > 500 μg /l)
  3. Incidence of any severe gastrointestinal symptoms (Mucositis, Enterocolitis, Typhlitis, Nausea, Diarrhea)
  4. Not willing to continue treatment.

Relevance to patient case: not relevant
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: Identification of New Immune Factors Specific of Relapse in Childhood B Lineage Acute Lymphoblastic Leukemia

Summary: B-acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Despite enhancement of childhood B-ALL outcome, relapses remain difficult to treat. Several studies in adult acute myeloid leukaemia have shown that proliferation of immunosuppressive cells -particularly T regulatory (Treg) cells and deficient natural killer (NK) cells- was associated with poor response to chemotherapy. However, few studies have been done on childhood ALL and none on relapse of B-ALL. Moreover, a newly described immunosuppressive B cells subset (Breg cells) seems to have a role in oncogenesis in mice model, but its significance has never been evaluated in human cancers. The purpose of this study is to prospectively evaluate the immune status of children newly diagnosed with first relapse of B-cell ALL, and to compare results with those of children treated for B-ALL in complete remission. Classic lymphocytic phenotype, proportions of immunosuppressive cells (Treg cells, deficient NK cells, Cytotoxic T-lymphocyte-associated protein 4 and/or Programmed T cell death 1) and thymopoiesis will be evaluated. The investigators assume that increase of immunosuppressive cells proportions could be associated with B-ALL relapse.


Eligibility: 1. Inclusion Criteria for relapse Group :
  -  Children aged from 1 to 18 years at the time of first B-ALL relapse diagnosis
  -  Obtention of oral and written consent of the parents
  -  Parents affiliated with the social security system
  2. Inclusion Criteria for control Group :
  -  Children aged from 1 to 18 years enrolled into FRALLE or EORTC treatment protocols, treated for B-ALL and who are in complete molecular remission
  -  Obtention of oral and written consent of the parents
  -  Parents affiliated with the social security system
  3. Exclusion criteria for control Group are the same as for relapsed Group :
  -  Children with hematologic syndrome predisposing to hematologic neoplasia (such as Fanconi's anaemia, Diamond Blackfan anaemia …) or acute leukemia secondary to previous treatment, or who have had allogenic hematopoietic stem cell transplantation before relapse

Relevance to patient case: not relevant
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: Safety and Efficiency Study of Pioglitazone in Combination With Imatinib Mesylate to Treat Chronic Myelogenous Leukemia

Summary: The purpose of this study is to assess the safety and efficiency of adding pioglitazone to chronic phase chronic myelogenous leukemia patients having received imatinib mesylate who have acquired a stable molecular response but not complete molecular response.

Detailed description: Although tyrosine-kinase inhibitors have profoundly converted the outcomes of chronic myelogenous leukemia patients ,the most of who could have a complete cytogenetic response, a large majority of patients could not come to a complete molecular response that is undetectable in breakpoint cluster region-Abelson chimeric oncogene transcripts. According to some previous researches, pioglitazone may target leukemia stem cells and induce them into cell cycle making them exit from quiescent undivided states. Subsequently, pioglitazone may gradually erode leukemia stem cells leading to undetectable minimal residual disease. Thus the investigators expect to assess the safety and efficiency of pioglitazone in combination with imatinib mesylate in clinical trials. Maybe the combination therapy induce more patients in a detectable molecular response into a deeper molecular response. Furthermore, pioglitazone may be extensively adapted into the treatment of chronic phase chronic myelogenous leukemia patients as a common protocol.

Eligibility: Inclusion Criteria:
  1. Signed informed consent.
  2. Treatment with imatinib mesylate for more than 2 years.
  3. Patients with chronic phase chronic myelogenous leukemia having a complete cytogenetic response and a stable molecular response without complete molecular response.
  4. Normal important organs such as kidney, liver and heart.
  Exclusion Criteria:
  1. Severe important organs disfunction such as liver and kidney.
  2. Cardiovascular disease.
  3. Osteoporosis in therapy.
  4. Severe fluid retention.

Relevance to patient case: not relevant
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: Allogeneic Stem Cell Transplantation for Children With CML

Summary: In children and adolescents with chronic myeloid leukaemia (CML) stem cell transplantation (SCT) may be a valid alternative to the life-long treatment with tyrosinkinase inhibitors (TKI). This trial aims to evaluate the use of a reduced intensity conditioning regimen (RIC), consisting of fludarabine, melphalan and thiotepa in order to minimize transplant related mortality and toxic late effects. Strict post-transplant monitoring and reintroduction of TKI as well as donor lymphocyte infusions (DLI) in case of relevant residual disease are part of the protocol.

Detailed description: Chronic myeloid leukaemia (CML) is a rare disease in children with an incidence of 3-5% of all paediatric leukaemias. Since the introduction of tyrosinkinase inhibitors (TKI) stem cell transplantation (SCT) is no longer the first choice treatment for patients with early phase CML.
  However life-long treatment with TKI may not be feasable in several cases due to side effects such as growth retardation, non-compliance and resistance. This protocol evaluates the feasibility of SCT following a reduced intensity conditioning regimen (RIC) consisting of fludarabine, melphalan, thiotepa and thymoglobuline (ATG). Matched siblings and matched unrelated donors are permitted for stem cell donation. In case of unrelated donors tissue typing has to be done by high resolution molecular typing. Donors with 10/10 or 9/10 identical allels in the human leukocyte antigen (HLA) system are accepted. Preferred stem cell source is bone marrow but peripheral blood stem cells and umbilical cord blood are also allowed. Graft-versus-Host-Disease (GvHD)-prophylaxis is achieved with cyclosporine A and mycophenolate mofetil.
  Monitoring of the breakpoint cluster region - Abelson (BCR/ABL) rearrangement is performed monthly in the first year after SCT. In case of BCR/ABL positivity TKI are given in the first year after SCT. Followed by donor lymphocyte infusions (DLI) later on if BCR/ABL positivity persists.

Eligibility: Inclusion Criteria:
  -  children and adolescents with BCR/ABL positive CML in chronic phase, who are eligible for allogeneic stem cell transplantation, irrespective of the previous treatment strategy
  -  availability of a HLA matched sibling donor (MSD), a matched family donor, a matched unrelated donor or a matched unrelated cord blood (MD)
  -  informed consent
  Exclusion Criteria:
  -  unavailability of MSD or MD
  -  patients in accelerated phase or blast crisis
  -  pregnancy
  -  previous autologous or allogeneic SCT
  -  no informed consent

Relevance to patient case: definitely relevant
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: Dasatinib or Nilotinib Followed by Imatinib in Patients With Newly Diagnosed, Chronic Phase Chronic Myeloid Leukemia

Summary: This phase II trial studies how well dasatinib, nilotinib, and imatinib mesylate works in treating patients with newly diagnosed, previously untreated chronic myeloid leukemia in which fewer than 10% of the cells in the blood and bone marrow are blast cells (immature blood cells) (chronic phase). Dasatinib, nilotinib, and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description: PRIMARY OBJECTIVES:
  I. To assess incidence of major molecular response (MMR) at 12 months.
  SECONDARY OBJECTIVES:
  I. To assess progression free survival (PFS) at 12 and 24 months.
  II. To assess accelerated phase (AP) or blast phase (BP) transformation-free survival at 12 and 24 months.
  III. To assess incidence of deep MRs (≥ MR⁴) at 12 months and 24 months.
  IV. To assess safety.
  V. To assess patient reported outcomes (PRO).
  TERTIARY OBJECTIVES:
  I. To assess prognostic significance of detecting aberrant myeloid or lymphoid markers on diagnostic bone marrow.
  II. To assess ability to enroll subjects who maintain deep molecular remissions in tyrosine kinase inhibitors (TKIs) discontinuation trials.
  OUTLINE:
  Patients receive dasatinib orally (PO) once a day (QD) or nilotinib PO twice a day (BID) at the discretion of the treating hematologist. Patients achieving either a 1 log reduction at 3 months or a 2 log reduction at 6 months in their breakpoint cluster region-abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) transcript levels may switch to imatinib mesylate PO QD.
  After completion of study treatment, patients are followed up at 2 weeks and then up to 60 months.

Eligibility: Inclusion Criteria:
  -  Newly diagnosed, previously untreated chronic phase chronic myeloid leukemia (CP-CML) (by World Health Organization [WHO] definition) (hydroxyurea permitted up to 7 days prior to enrollment)
  -  Clinically significant gastrointestinal disease, digestive dysfunction, or surgery that would compromise absorption of oral administration of medications
  -  Able to give written informed consent and comply with all study visits and procedures
  Exclusion Criteria:
  -  Chronic myeloid leukemia (CML) in AP or BP
  -  Unable to receive TKI for insurance reasons (uninsurable)
  -  Refuse or unable to perform telephone or video conferences with research nurse
  -  Subjects who are pregnant, breast feeding or sexually active and unwilling to use effective birth control while on treatment with TKI
  -  Any medical or psychological condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial, poses any additional risk for the subject, or confounds the assessment of the subject

Relevance to patient case: not relevant
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia

Summary: This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent chemotherapy regimen for the treatment of B-cell acute lymphoblastic leukemia. Part 1 of the study will optimize the dose of study drug (ruxolitinib) in combination with the chemotherapy regimen. Part 2 will evaluate the efficacy of combination chemotherapy and ruxolitinib at the recommended dose determined in Part 1.


Eligibility: Inclusion Criteria:
  -  De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present at diagnosis:
  -  Age ≥ 10 years
  -  White blood cell (WBC) ≥ 50 × 10^3/μL
  -  CNS3 leukemia
  -  One of the following Ph-like ALL genetic lesions must be present in the diagnostic bone marrow or peripheral blood sample:
  -  CRLF2 rearrangement with JAK1 or JAK2 mutation (JAK+)
  -  CRLF2 rearrangement without JAK mutation
  -  Other JAK pathway alterations (eg, JAK2 fusions, erythropoietin receptor (EPO-R) fusions, SH2B3 deletions, interleukin-7 receptor-alpha (IL7RA) mutations) with or without CRLF2 rearrangement
  -  Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or as the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed
  -  Male and female subjects of reproductive non childbearing potential or willing to take appropriate precautions to avoid pregnancy or fathering a child for the duration of study participation
  Exclusion Criteria:
  -  Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment
  -  Trisomy 21 (Down syndrome)
  -  BCR-ABL1-rearranged (Ph+) ALL
  -  Calculated creatinine clearance or radioisotope glomerular filtration rate < 70 mL/min/1.73 m^2
  -  Alanine aminotransferase ≥ 3 × upper limit of normal (ULN) for age
  -  Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN)
  -  History or evidence of cirrhosis
  -  Platelet count < 75 × 10^3/μL
  -  Absolute neutrophil count (ANC) < 750/μL
  -  Positive screen for hepatitis B or C
  -  Known human immunodeficiency virus infection

Relevance to patient case: not relevant
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: Transplantation of Ex Vivo Expanded, UCB-derived, Stem & Progenitor Cells vs. Unmanipulated UCB for HM Patients

Summary: This study is an open-label, controlled, multicenter, international, Phase III, randomized study of transplantation of NiCord® versus transplantation of one or two unmanipulated, unrelated cord blood units in patients with acute lymphoblastic leukemia or acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia, all with required disease features rendering them eligible for allogeneic transplantation.

Detailed description: Successful blood and marrow transplantation (BMT) requires the infusion of a sufficient number of hematopoietic stem/progenitor cells (HSPCs), capable of both homing to the bone marrow and regenerating a full array of hematopoietic cell lineages with early and late repopulating ability in a timely fashion.
  A major drawback of Umbilical Cord Blood (UCB) is the low stem cell dose available for transplantation, compared to mobilized peripheral blood (PB) or bone marrow. This low stem cell dose can compromise the chances of engraftment and contributes to delayed kinetics of neutrophil and platelet recovery, as well as other transplant outcomes.
  The aim of ex vivo expansion of cord blood is to provide a graft with sufficient numbers of cells that have rapid and robust in vivo neutrophil and platelet producing potential to enable successful transplantation.
  NiCord® is a stem/progenitor cell-based product composed of ex vivo expanded allogeneic cells from one entire unit of UCB. NiCord® utilizes the small molecule nicotinamide (NAM), as an epigenetic approach to inhibit differentiation and to increase the migration, bone marrow (BM) homing and engraftment efficiency of Hematopoietic Progenitor Cells (HPC) expanded in ex vivo cultures. The chief aim of the study is to compare the safety and efficacy of NiCord® single ex-vivo expanded cord blood unit transplantation to unmanipulated cord blood unit transplantation in patients with hematological malignancies following conditioning therapy.

Eligibility: Inclusion Criteria:
  -  Applicable disease criteria
  -  Patients must have one or two partially HLA-matched CBUs
  -  Back-up stem cell source
  -  Adequate Karnofsky Performance score
  -  Sufficient physiological reserves
  -  Signed written informed consent
  Exclusion Criteria:
  -  HLA-matched donor able to donate
  -  Prior allogeneic HSCT
  -  Other active malignancy
  -  Active or uncontrolled infection
  -  Active/symptoms of central nervous system (CNS) disease
  -  Pregnancy or lactation

Relevance to patient case: not relevant
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: Long Term Effects of Tyrosine Kinase Inhibitor Therapy on Ovarian Reserve and Fertility in Patients With Chronic Myeloid Leukemia or Gastrointestinal Stromal Tumor

Summary: This pilot research trial studies the long term effects of tyrosine kinase inhibitor therapy on ovarian reserve and fertility in patients with chronic myeloid leukemia or gastrointestinal stromal tumor. Studying ovary imaging, ovarian reserve markers, and hormone levels from patients receiving tyrosine kinase inhibitor therapy may help doctors learn more about the effects of tyrosine kinase inhibitor therapy on ovarian function and fertility.

Detailed description: PRIMARY OBJECTIVES:
  I. To collect preliminary information to help design a study to look at longitudinal changes in markers of ovarian reserve and menstruation in premenopausal women undergoing tyrosine kinase inhibitors (TKI) therapy.
  SECONDARY OBJECTIVES:
  I. Evaluate ovarian response to controlled ovarian hyperstimulation in patients who elect to undergo in vitro fertilization (IVF) for fertility preservation.
  OUTLINE:
  Patients undergo transvaginal ultrasound for antral follicles analysis and collection of serum for ovarian reserve markers and hormonal analysis before TKI therapy and at 12, 24, and 48 weeks.

Eligibility: Inclusion Criteria:
  -  Diagnosed with chronic myeloid leukemia (CML), gastrointestinal stromal tumor (GIST), non metastatic cancer where TKI is the first line agent
  -  Premenopausal (has had menses at any time in the preceding 12 consecutive months)
  -  Has not undergone a hysterectomy or bilateral oophorectomy
  -  Willing to use non-hormonal (ie: barrier method or abstinence) as form of contraception during the one year of study
  Exclusion Criteria:
  -  Patients who have had chemotherapy or radiotherapy in the past
  -  Patients may not be receiving any other investigational agents
  -  Patients must not be pregnant or nursing
  -  Other medical conditions or treatments that affect hormonal levels (potentially confounding interpretation of results)
  -  Patients with ongoing hormonal contraception or unwilling or unable to discontinue will not eligible

Relevance to patient case: not relevant
Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: Haploidentical Hematopoietic Stem Cell Transplantation for Acute Leukemias

Summary: This is a prospective observational cohort study of haploidentical transplantation with post-transplant cyclophosphamide for acute leukemias using reduced intensity conditioning for acute myeloid leukemia (AML) and myeloablative conditioning for acute lymphoblastic leukemia (ALL).

Detailed description: Hematopoietic stem cell transplantation (HSCT) is the most effective treatment for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), with the lowest rates of relapse.
  Fertility rate in Brazil is falling, and only 25% of people born today will have a matched sibling donor. On the other hand, currently donor non-related to about 50% of patients enrolled in Brazilian Receptor Registry (REREME). Consequently, at least 35% of patients won't have a matched donor.
  The haploidentical transplantation is defined as a partially matched hematopoietic cell transplantation, using a partially matched family donor (parent, sibling or child). Haploidentical transplantation activity is growing worldwide, with results comparable matched unrelated donors.
  The objective of this study is to test the feasibility of haploidentical transplantation with post transplant cyclophosphamide for acute leukemias in a Brazil.

Eligibility: Inclusion Criteria:
  -  Acute lymphoblastic leukemia or acute myeloid leukemia
  Exclusion Criteria:
  -  Severe comorbidities
  -  Second transplant

Relevance to patient case: not relevant