Oncology

Source: View full study details on ClinicalTrials.gov

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Source: View full study details on ClinicalTrials.gov

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Source: View full study details on ClinicalTrials.gov

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Source: View full study details on ClinicalTrials.gov

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Inclusion Criteria:

• Diagnosis of recurrent, unresectable, or metastatic DDLPS

  • The definition of recurrent disease is a patient with a primary tumor that has been successfully resected, but has recurred after primary surgery
  • Any number of prior systemic therapies will be allowed
• Age ≥ 18 years at the time of informed consent
• Willing and able to provide written informed consent/assent for the trial
• Willing to comply with treatment protocol
• Adequate performance status: Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1/Karnofsky Performance Status (KPS) 70-100%

• Presence of measurable disease per RECIST v1.1

  o Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression

• QTc ≤ 480 msec using Fredericia’s QT correction formula

• Adequate organ function determined within 2 weeks of treatment initiation, defined as follows:

  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count ≥ 1,500/mm3 (1.0 x 109/L)
  • Platelet count ≥ 75,000/mm3 (50 x 109/L)
  • Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for a patient with total bilirubin level > 1.5 x ULN
  • Aspartate aminotransferase (AST) ≤ 2.5 x ULN OR ≤ 5 x ULN for patients with liver metastases
  • Alanine aminotransferase (ALT) ≤ 2.5 x ULN OR ≤ 5 x ULN for patients with liver metastases
  • Alkaline phosphatase < 5 x ULN

  • Serum creatinine ≤ 1.5 x ULN or a measured or calculated creatinine clearancea

    ≥ 60 mL/min for a patient with creatinine levels > 1.5 x institutional ULN (Note: Creatinine clearance need not be determined if the baseline serum creatinine is within normal limits. GFR can also be used in place of creatinine or CrCl)

  • International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT and PTT is within therapeutic range of intended use of anticoagulants
• For female patients of childbearing potential, negative serum pregnancy test at screening visit and within 72 h prior to the first dose of study medication

aCreatinine clearance should be calculated per institutional standard.

Contraception Requirements

Female participants of reproductive potential and male participants with female partners of reproductive potential are required to use highly effective contraceptive measures from the first dose of study treatment until 30 days after the last dose of etrumadenant or 90 days after the last dose of zimberelimab, whichever is longer.

Highly effective contraception is defined as use of one or more methods that result in a low failure rate (i.e., less than 1%). Highly effective contraceptive measures include:

• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
• Progestogen only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
• Intrauterine device
• Intrauterine hormone-releasing system in combination with a barrier method (preferably male condom)

• Surgical sterilization

  • Female participant or female partner of the male participant has undergone bilateral tubal ligation
  • Male participant is vasectomized (with documented medical confirmation of surgical success) and is the sole sexual partner of a female with reproductive potential
• Complete sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant

To ensure proper birth control, female participants who use hormonal contraception should use an efficient barrier contraceptive (condom plus spermicide). Additionally, male participants, when having sexual intercourse with a female of reproductive potential, should use an efficient barrier contraceptive (condom plus spermicide); the respective partner should also use an additional efficient contraceptive method (e.g., oral pills, intrauterine device, or diaphragm, and spermicide).

Exclusion Criteria:

Patients who fulfil any of the following criteria are not eligible for admission to the study:

• Prior treatment with systemic PD-1 or PD-L1 inhibitor
• Prior treatment with an agent targeting the adenosine pathway

• Have a concurrent unrelated malignancy that requires active treatment

  o Patients with concurrent malignancies of a different tumor whose natural history or treatment will likely not interfere with the safety or efficacy assessment of the investigational drug will be eligible

• Uncontrolled intercurrent illness including active infection requiring systemic therapy or symptomatic congestive heart failure within the past 6 months

• Has known active central nervous system (CNS) metastases

  • Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to study Day 1 and return to baseline of neurologic symptoms), and have no evidence of new or enlarging brain metastases. This exception does not include sarcomatous meningitis, which is excluded regardless of clinical stability.
  • Patients must be on a stable or decreasing corticosteroid dose at the time of study entry; patients who require escalating doses of corticosteroids for the treatment of CNS metastases will be excluded.

• Shows evidence of clinically significant immunosuppression such as the following:

  • Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
  • Concurrent opportunistic infection
  • Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses > 10 mg/day of prednisone or equivalent within 14 days prior to enrollment. However, in the setting of non-immune mediated indications for use, chronic/active low dose steroid use may be permitted at the discretion of the principal investigator.

• Has a known infection with HIV AND

  • CD4+ T-cell (CD4+) counts < 350 cells/uL
  • An opportunistic infection within the prior 12 months

• Has a known active infection with hepatitis B or hepatitis C

  • Chronic carriers of HBV infection (HBsAg-positive, undetectable or low HBV DNA, and normal ALT) or individuals who have serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and anti-HBc-positive) may be eligible if suppressive antiviral therapy can be safely administered.
  • Patients who have completed curative antiviral treatment for HCV and have a viral load below the limit of quantification will be eligible (e.g. a patient who is HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution)
• Has a known history of active tuberculosis infection
• Has history or evidence of symptomatic autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in the past 2 years.

Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease.

Source: View full study details on ClinicalTrials.gov

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Lung cancer remains the most lethal malignancy in men and women in the U.S. Providing high quality management of these patients in the community setting as compared to hospital or academic centers offers the opportunity to reduce cost without sacrificing clinical outcome and simultaneously improving patient convenience and value. Many patients diagnosed with late-stage cancers can benefit from advanced biomarker testing, yet not all eligible patients receive this type of diagnostic testing today.

Within advanced non-small-cell lung cancer (aNSCLC), there are many specific somatic mutations observed in select patient populations that have targeted highly effective and less toxic therapies. National guidelines have advocated for broad tumor molecular profiling as a part of the standard diagnostic evaluation for aNSCLC, with the goal of identifying driver mutations for which effective therapies or clinical trials are available.

Furthermore, there is emerging evidence that molecular testing can impact treatment choices in earlier stages of lung cancer. However, adherence to genomic testing guidelines presents unique challenges to community oncologists. While most oncology clinical research has been conducted at well-established academic medical centers, over 85% of cancer patients are diagnosed and treated at local, community-based clinical practices. Barriers exist in the ability to order these tests efficiently, in a timely manner, and reimbursed accordingly. Furthermore, patient care can vary drastically based on community-associated disparities.

This longitudinal clinical trial will generate Real World Evidence (RWE) to validate efficacy of first treatment regimen in newly diagnosed patients with non-small cell lung cancer. The MYLUNG Program integrates three separate protocols: Protocol #1 interrogated historical data from a large number of practices seeing lung cancer patients to evaluate biomarker testing, decision making patterns, the patient journey, and the tissue journey; Protocol #2 prospectively evaluated the patient journey in a limited number of index practices focused on testing; integration of testing results; and treatments. Interventional strategies to optimize these objectives will be developed and integrated into various interventions all aimed at improving biomarker testing rates. Protocol #3 (22285) will serve as a resource to monitor the impact of these strategies on the patient journey as it relates to shared decision making, and will continue to prospectively evaluate the patient journey in a limited number of index practices focused on testing, integration of testing results and treatments.

Source: View full study details on ClinicalTrials.gov

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Inclusion Criteria:

II. Acute lymphoblastic leukemia (ALL):

III. Other acute leukemias: Acute leukemias of ambiguous lineage or mixed phenotype with less than 5% blasts. Leukemias in morphologic remission with persistent cytogenetic, flow cytometric or molecular aberrations are eligible.

IV. Myelodysplastic Syndromes (MDS) and Myeloproliferative Disorders (MPD) other than myelofibrosis:

• International prognostic scoring system (IPSS) risk score of INT-2 or high risk at the time of diagnosis.
• Any IPSS risk category if life-threatening cytopenia(s) exists.
• Any IPSS risk category with karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia.
• MDS/MPD overlap syndromes without myelofibrosis.
• MDS/ MPD patients must have less than 10% bone marrow myeloblasts and ANC > 0.2 (growth factor supported if necessary) at transplant work-up.

V. Non-Hodgkin lymphoma (NHL) at high-risk of relapse or progression if not in remission:

Eligible patients with aggressive histologies (such as, but not limited to, diffuse large B-cell NHL, mantle cell NHL, and T-cell histologies) in CR by PET/CT imaging.

o Eligible patients with indolent B-cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) will have 2 nd or subsequent progression with PR or CR by PET/CT imaging.

VI. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) in morphologic remission.

Prior treatment:

To prevent graft rejection, patients who received only non-lymphodepleting agents for their malignancy (hypomethylating agents, venetoclax, hydroxyurea, TKIs etc.), or patients who received lymphodepleting chemotherapy > 3 months prior to scheduled admission, should receive fludarabine 25 mg/m2 daily x 3 days for lymphodepletion 14-42 days (aiming for 2-4 weeks) prior to admission in order to qualify for the protocol.

Organ Function and Performance Status Criteria:

• Karnofsky score equal or greater than 80% (See Appendix B; inpatient Leukemia service transfers without discharge are acceptable provided patient has equivalent KPS as if were outpatient).
• Calculated creatinine clearance > 70 ml/min.
• Bilirubin < 1.5 mg/dL (unless benign congenital hyperbilirubinemia or hemolysis).
• ALT < 3 x upper limit of normal (ULN).
• Pulmonary function (spirometry and corrected DLCO) > 60% predicted.
• Left ventricular ejection fraction > 50%.
• Albumin > 3.0.
• Hematopoietic Cell Transplantation Comorbidity index (HCT-CI) ≤5.

Graft criteria:

Two CB units will be selected according to current MSKCC CB unit selection algorithm. High resolution 8-allele HLA typing and recipient HLA antibody profile will be performed. Unit selection will occur based on HLA-match, total nucleated cell (TNC) and CD34+ cell dose adjusted per patient body weight. The bank of origin will also be considered. Donor specific HLA antibodies, if present, will also be taken into consideration and may influence the selection of the graft.

• Each CB unit must be at least 3/8 HLA-matched to the patient considering high-resolution 8-allele HLA typing.
• Each CB unit will be required to have a cryopreserved TNC dose of at least 1.5 x 10^7 TNC/ recipient body weight (TNC/ kg).
• Each CB unit will be required to have a cryopreserved CD34+ cell dose of at least 1.5 x 10^5 CD34+ cells/ recipient body weight (CD34+ cells/kg).
• A minimum of one unit will be reserved as a backup graft.
• Each CB unit will be required to be cryopreserved in standard cryovolume (24-27 ml/s per unit or per bag if unit in two bags) and be red blood cell depleted.

Exclusion Criteria:

• Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis.
• Patients persistent with CNS involvement in CSF or CNS imaging at time of screening
• Prior checkpoint inhibitors/ blockade in the last 12 months.
• Two prior stem cell transplants of any kind.
• One prior autologous stem cell transplant within the preceding 12 months.
• Prior allogeneic transplantation.
• Prior involved field radiation therapy that would preclude safe delivery of 400cGy TBI in the opinion of Radiation Oncology.
• Active and uncontrolled infection at time of transplantation.
• HIV infection.
• Seropositivity for HTLV-1.
• Inadequate performance status/ organ function.
• Pregnancy or breast feeding.
• Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, long-term follow-up, and research tests.

Source: View full study details on ClinicalTrials.gov

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Source: View full study details on ClinicalTrials.gov

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Primary Objective:

–Evaluate the impact of an organized, longitudinal, diet and exercise training program on fatigue as assessed by the Functional Assessment of Cancer Therapy (FACT) score in patients with CLL.

Secondary Objectives:

–Assess changes in physical activity, dietary behavior, physical function using the PROMIS physical function questionnaire and performance tests of physical function, body mass index (BMI) and global quality of life. Additionally, we will assess changes in fecal microbiome composition, metabolic parameters including a comprehensive lipid panel, glucose, insulin, TNF alpha, IL6, leptin, resistin, adiponectin, IGF1 and IGFBP1 and immunologic function as assessed by T cell and monocyte phenotypic and functional assays in patients with CLL after participation in the behavioral intervention.

Exploratory Objectives:

— Identify differences in the metabolic, immunologic and fecal microbiome composition in patients with CLL who have a high CLL comorbidity index score (CLL-CI) compared to patients with CLL and a low CLL-CI score. And, investigate the association of comorbidity score, disease features, CLL-specific prognostic factors and clinical outcomes.

Source: View full study details on ClinicalTrials.gov

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.