OncoTrials - мониторинг клинических исследований

Описание

Drug-free, single-center, prospective observational pilot study in hairy Cell Leukemia patients

Критерии включения

• 1. Histologically confirmed diagnosis of HCL patients:
• 1. newly diagnosed and candidates for first-line cytoreductive treatment with analogues purines or
• 2. in relapse after a previous line of treatment, with indication for rescue therapy (repetition of a purine analogue; use of targeted or innovative drugs), except splenectomy or
• 3. in CR for at least 5 years after a first line of treatment, in the absence of clinical alterations indicative of a state of hematological relapse, or in any case in the absence of an indication for a new line of cytoreductive therapy (time-to-next treatment exceeding 5 years).
• 2. Age ≥ 18 years at enrollment
• 3. Signature of written informed consent

Критерии исключения

• 1. Concomitant second malignancy.

Описание

This is a national multi-centre, experimental, cross-sectional, non-profit study.

Критерии включения

• for patients:
• * WHO2022-defined diagnosis of Hairy Cell Leukemia.
• * Age ≥18 years.
• * Signed informed consent.
• Inclusion criteria for Healthy Donors:
• * Age ≥18 years.
• * Volunteers in general good health, free from any disease or serious illness.
• * Signed informed consent.

Критерии исключения

• - None

Описание

Check whether patients with Hairy Cell Leukemia (HCL) of different status (at diagnosis, in complete remission /> 2 years or relapsed requiring therapy) have a `signature` of altered immunity based on extracellular vesicles (EV)

Критерии включения

• for patients:
• * WHO2022-defined diagnosis of Hairy Cell Leukemia.
• * age ≥18 years.
• * signed informed consent.
• Inclusion criteria for Healthy Donors:
• * age ≥18 years.
• * Volunteers in general good health, free from any disease or serious illness.
• * Signed informed consent.

Критерии исключения

• - None

Описание

The researchers are doing this study to compare the safety of vemurafenib in combination with obinutuzumab to the standard of approach of cladribine in combination with rituximab. The researchers will look at which treatment causes fewer or milder side effects. Researchers think vemurafenib and obinutuzumab (non-chemotherapy drugs) may cause fewer side effects compared with the usual approach of chemotherapy drugs. They will also compare the two approaches to see which approach is more effective at eliminating cancer cells.

Критерии включения

• * Patients must be ≥ 18 years of age
• * Histologically confirmed classical HCL by the enrolling institution
• * Presence of BRAF V600E mutation as confirmed by PCR, NGS or immunohistochemistry. If patient is known to have negative BRAF mutation, repeat testing is advisable as well as discussion with the main study principal investigator.
• * Has not received any prior therapy for the disease
• * Patients who meet the standard treatment initiation criteria, as defined by ANC ≤1.0, Hgb ≤ 10.0 or PLT ≤100K
• * ECOG performance status of 0 - 2
• * Acceptable pre-study organ function during screening as defined as:
• * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
• * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN; and
• * Serum creatinine ≤ 1.5x ULN
• * Electrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or ischemia as determined by the investigator and a rate-corrected QT interval (QTc, Bazett`s formula) of /< 480 msec
• * For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of vemurafenib and cladribine, and 18 months after discontinuation of rituximab and obinutuzumab
• * For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of vemurafenib
• * Negative serum pregnancy test within 7 days of commencement of treatment in women of childbearing potential

Критерии исключения

• * Have had previous treatment for HCL, including purine analogs, vemurafenib, rituximab, obinutuzumab, and other investigational agents. Previous treatment with transfusions and other supportive care such as G-CSF and erythropoietin are allowed.
• * Known hypersensitivity to any of the study drugs.
• * Patients with known long QT syndrome or uncorrectable electrolyte abnormalities
• * Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
• * Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody
• ° Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody /[HBcAb/] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing and take HBV viral prophylaxis such as entecavir.
• * Known infection with HIV or human T-cell leukemia virus 1 (HTLV-1)
• * Active uncontrolled infection, e.g. persistent bacteremia, supplemental oxygen or pressor supports, etc.
• * Live vaccination within 28 days of randomization
• * Patients with concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of the skin, in situ cervical cancer, adequately treated stage I/II cancer from which the patient is current in complete remission, or any other cancer from which the patient has been disease free for five years
• * Malabsorption syndrome or other condition that precludes enteral route of administration
• * Patients with HCL variant (as defined by absence of expression of CD25)
• * Pregnant or lactating, or intending to become pregnant during the study

Описание

This phase II trial tests how well venetoclax works in treating patients with hairy cell leukemia that has come back after a period of improvement (relapsed). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival.

Критерии включения

• * Patients must have histologically or cytologically confirmed HCL/HCLv after purine analog therapy who are relapsed from or are ineligible for BRAF therapy and have not received prior venetoclax
• * Age ≥ 18 years
• * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• * Total bilirubin ≤ 3 x institutional upper limit of normal (ULN) unless consistent with Gilbert`s (ration between total and direct bilirubin /> 5)
• * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase /[SGOT/])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase /[SGPT/]) ≤ 3 × institutional ULN
• * Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 45 mL/min/1.73m/^2
• * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• * Patients must have had no HCL/HCLv treatment for ≥ 4 weeks prior to enrollment, and those with treatment /> 4 weeks prior to enrollment must not be responding to their last treatment with decreasing tumor burden or improving drug-related cytopenias
• * Patients must have a need for treatment due to absolute neutrophil count (ANC) /< 1/nL, hemoglobin (Hgb) /< 10g/dL, platelets (Plt) /< 100/nL, symptomatic splenomegaly, enlarging HCL mass /> 2cm in short axis, enlarging HCL mass /> 0.5 cm in the central nervous system (CNS) in short axis, or leukemic count /> 5/nL
• * The effects of venetoclax on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during treatment and for 30 days after the last dose of venetoclax. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception during treatment and for 30 days after the last dose of venetoclax
• * Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
• * Ability and willingness to swallow pills

Критерии исключения

• * Patients who have received prior venetoclax
• * Patients who are receiving any other investigational agents
• * History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax
• * Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
• * Pregnant women are excluded from this study because venetoclax is a B-cell lymphoma-2 (BCL-2) inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued if the mother is treated with venetoclax
• * Malabsorption syndrome or other conditions that would interfere with intestinal absorption
• * Live attenuated vaccines should not be administered within 4 weeks prior to, during, or 30 days after study treatment and recovery has occurred