ALL Backbone in AYAs

Официальное название

Treatment of Newly Diagnosed Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in Adolescents and Young Adults (AYAs)

Обзор

The goal of this research study is to evaluate a chemotherapy regiment for the treatment of newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs). The names of the study drugs involved in this study are: * blinatumomab (a type of immunotherapy drug) * cyclophosphamide (a type of chemotherapy drug) * cytarabine (a type of antineoplastic agent) * dexamethasone (a type of synthetic glucocorticoid) * doxorubicin (a type of antineoplastic agent) * etoposide (a type of antineoplastic agent) * mercaptopurine (a type of antineoplastic agent) * methotrexate (a type of chemotherapy drug) * pegaspargase (a type of antineoplastic agent) * vincristine (a type of antineoplastic agent)

Подробное описание

This Phase 2, single-arm research study is to evaluate a chemotherapy regiment the treatment of newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs).

The U.S. Food and Drug Administration (FDA) has approved all of the drugs of treatment being studied but the investigators of this research study want to understand more about the safety and effectiveness of the chemotherapy regimen in adolescents and young adults with newly diagnosed Philadelphia chromosome-negative ALL.

The research study procedures include screening for eligibility, in-clinic visits, blood tests, urine tests, saliva tests, X-rays, electrocardiograms (ECGs), echocardiograms (ECHOs), Dual-Energy X-ray Absorptiometry (DEXA) scans, bone marrow aspirations/biopsies.

Participation in this study is expected to last about 10 years, 2 years of treatment followed by 8 years of follow up.

It is expected that about 67 people will take part in this research study.

Вмешательства

• Препарат Blinatumomab
  A bispecific T-cell engager (BiTE) antibody, single-use vial via intravenous infusion, per standard of care
• Препарат Oncaspar
  A modified enzyme L-asparaginase, single-use vial via intravenous infusion, per standard of care
• Препарат Cyclophosphamide
  An alkylating agent, single-use vial via intravenous infusion, per standard of care
• Препарат Cytarabine
  An antineoplastic antimetabolite, multi-dose vial via intrathecal injection (through the spinal space), per standard of care
• Препарат Dexamethasone
  A synthetic glucocorticoid, tablets or single-use vials via orally or intravenous infusion (through the vein), per standard of care
• Препарат Doxorubicin Hydrochloride
  An anthracycline antibiotic, single-use or multi-dose vials via intravenous infusion, per standard of care
• Препарат Etoposide
  A derivative of podophyllotoxin, multi-dose vial via intravenous infusion, per standard of care
• Препарат Mercaptopurine
  A purine antagonist, tablet via orally, per standard of care
• Препарат Methotrexate
  A folate analogue, multi-dose and single-use vials via intrathecal injection, per standard of care
• Препарат Vincristine
  A vinca alkaloid, single-use vials via intravenous injection, per standard of care

Первичные конечные точки

• Treatment Completion Rate Through Time Point 3 (TP3) [Срок оценки: Timeframe for TP3 depends on disease immunophenotype. Participants with CD19-positive B-ALL, TP3 occurs at the end of Blinatumomab Cycle 2 on Day 28 (130 days from study start). For participants with T-cell ALL or those who do not receive blinatum]

Вторичные конечные точки (12)

• Rate of Treatment-Related Mortality (TRM) [Срок оценки: Up to 115 weeks]
• Rate of Treatment Discontinuation due to Toxicity or Disease [Срок оценки: Up to 115 weeks]
• Rate of Asparaginase Non-Completion [Срок оценки: This endpoint is assessed during Consolidation II, which occurs approximately from Day 270 to Day 480 of study treatment.]
• Reason of Asparaginase Non-Completion [Срок оценки: Up to 115 weeks]
• Grade 3 Infections Toxicity Rate [Срок оценки: Adverse events will be followed for 30 days after completion of protocol treatment, with the overall treatment period up to 115 weeks.]
• Grade 3 Asparaginase-associated Toxicities Rate [Срок оценки: Adverse events will be followed for 30 days after completion of protocol treatment, with the overall treatment period up to 115 weeks.]
• Grade 3 Orthopedic Toxicity Rate [Срок оценки: Adverse events will be followed for 30 days after completion of protocol treatment, with the overall treatment period up to 115 weeks. Ostenonecrosis and fractures will be followed up to 10 years.]
• Complete remission Rate (CRR) [Срок оценки: CR can be documented either at the end of Induction IA (32 days) or Induction IB (74 days).]
• Measurable Residual Disease (MRD) Negativity Rate at the end of Induction IA (Time Point 1) [Срок оценки: At the end of Induction IA (32 days from study start)]
• Measurable Residual Disease (MRD) Negativity Rate at the end of Induction IB (Time Point 2) [Срок оценки: At the end of Induction IB (74 days from study start)]
• Measurable Residual Disease (MRD) Negativity Rate at Time Point 3 (TP3) [Срок оценки: For CD19-positive B-ALL, TP3 is reached at the end of Blinatumomab Cycle 2 on Day 28 (Day 130 from study start). For T-cell ALL or participants not receiving blinatumomab, TP3 occurs on Day 28 of Consolidation IC (Day 102 from study start).]
• Median Event-Free Survival (EFS) [Срок оценки: Up to 10 years]

Критерии участия

Критерии включения

3.1.1Confirmed diagnosis of Philadelphia chromosome-negative acute lymphoblastic leukemia.

• Diagnosis should be made by peripheral blood, bone marrow aspirate, bone marrow biopsy, or tissue biopsy demonstrating ≥25% involvement by lymphoblasts, with flow cytometry or immunohistochemistry confirming B-ALL or T-ALL.

o Participants with B-cell and T-cell lymphoblastic lymphoma are eligible regardless of bone marrow involvement Participants with mixed phenotype acute leukemia (MPAL) ARE eligible, if an ALL regimen is felt to be most appropriate treatment.

• Participants with CNS leukemia ARE eligible. 3.1.2 Allowed prior therapy:
• Corticosteroids, hydroxyurea, all-trans retinoic acid (ATRA).
• IT chemotherapy.
• Emergent radiation therapy or leukapheresis for life threatening complications.
• One cycle of prior chemotherapy (i.e. an induction cycle given at another institution and participant transfers care for post-induction treatment; OR a participant does not meet eligibility prior to induction but does meet eligibility after remission induction).

3.1.3 Age 18.00 - 50.99 years 3.1.4 Direct bilirubin <1.4 mg/dL (total bilirubin < 1.4 mg/dL is acceptable). 3.1.5 Willingness to use effective means of birth control. The effects of chemotherapy on the developing human fetus are unknown. For this reason and because therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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 prior to the study, for the duration of study participation, and 4 months after completion of study.

3.1.6 Ability to understand and the willingness to sign a written informed consent document.

Критерии исключения

Philadelphia chromosome-positive / BCR::ABL1 fusion 3.2.2 Participants with mature B-cell (Burkitt's) ALL. Mature B-cell ALL is defined by the presence of surface immunoglobulin AND any of the following: t(8;14)(q24;q32), t(8;22), t(2;8), or c-myc-gene rearrangement by FISH, PCR or other testing. \[FISH/PCR testing for c-myc rearrangements is not required prior to study entry, but it is suggested for participants with surface immunoglobulin expression or L3 morphology\]. 3.2.3 Participants with acute undifferentiated leukemia. 3.2.4 Participants receiving any other investigational agent for this condition.

3.2.5 Uncontrolled intercurrent illness including but not limited to ongoing infection with vital sign instability (hypotension, respiratory insufficiency), life-threatening acute tumor lysis syndrome (e.g., with renal failure), symptomatic congestive heart failure, cardiac arrhythmia, intracranial or other uncontrolled bleeding. Circumstances that may significantly interfere with a participant's ability to safely comply with study procedures, such as attend scheduled study visits, adhere to treatment protocols, or complete study assessments. These include a lack of reliable transportation, unstable housing, or psychiatric illness, but reasonable attempts should be made to overcome these circumstances, including but not limited to identifying sponsor, institutional, or thirdparty financial or social support as well as psychiatric consultation for objective assessment. 3.2.6 Sexually active participants of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation are ineligible.

3.2.7 Pregnant women are excluded from this study because many of the agents used on this protocol have 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 these chemotherapy agents, breastfeeding should be discontinued if the mother is enrolled.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07227584 · 25-533

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗