Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Patients will receive 12-week induction Lorlatinib followed by radical surgery or local radiotherapy or continue Lorlatinib through MDT and optional consolidation lorlatinib for up to 2 years.

Patients were assigned to receive oral lorlatinib at a dose of 100 mg daily in a course of treatment that was measured in cycles of 28 days. 3 cycles of induction treatment will be required for the study.

Lorlatinib

Wen-Zhao Zhong, MD.

Chao Zhang, MD.

Ben-Yuan Jiang, MD.

A prospective, single-arm, open-label phase 2 study that evaluates the efficacy and safety of induction Lorlatinib in stage III non-small cell lung cancer and explores the clinical feasibility of dynamic ctDNA and multidisciplinary assessment in guiding local treatments.

Simon two-stage was applied to estimate the required sample size for the study. Overall an estimated 43 patients were required and at least 12 patients achieved pathological complete response would be deemed as positive result. Patients will be provided 3 cycles induction Lorlatinib 100mg and then assessed whether patients would be eligible for radical surgery or local radiotherapy through multidisciplinary evaluation. After local intervention, patients could choose consolidation treatment of Lorlatinib for up to 2 years or adjuvant doublet chemotherapy for up to 4 cycles. Dynamic blood samples will be collected before and after induction Lorlatinib as well as consolidation treatment. The primary endpoints is pCR for patients who received radical surgery.

A Simon two-stage design was applied. Primary endpoint for this study was pCR. The unacceptable response rate for pCR was less than 20% and desirable response rate was 40%. The error rate for alpha was set as 0.05 and 0.2 for beta. The Optimal assay was chosen and 43 patients were to be enrolled to meet adequate statical power. 13 patients would be enrolled in stage I and at least 3 patients achieved pCR were required to proceed stage II enrollment. Overall, if 12 patients achieved pCR, the study would be determined as positive. 10% drop-off rate should be considered and at least 48 patients should be enrolled.

Induction Lorlatinib in Stage III Non-small Cell Lung Cancer

Induction Lorlatinib for ALK Fusion Locally Advanced Non-small Cell Lung Cancer: A Prospective, Single Arm, Open-label Phase 2 Study

Partial clinicopathological data of participants will be presented in the corresponding manuscript.

The pathological complete response is defined as the absence of residual tumor in both lung and regional lymph nodes after induction treatment and radical surgery.

The period after initiation of induction treatment till the time of disease progress or any cause of death.

ORR is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of enrolled participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions.

The period after radical surgery till the time of disease relapse with either local recurrence or distant metastasis.

The exploratory ctDNA alteration will be stratified into three parts. 1) Induction period: overall ctDNA clearance rate (before and after induction treatment); 2) Posttreatment period: ctDNA clearance rate after local treatment; 3) Consolidation period: 1-year and 2-year ctDNA positive rate during consolidation treatment.

OS was assessed from initiation of treatment to death as a result of any cause.

Incidence of AE/SAE which has been confirmed correlation with Lorlatinib or local treatment.

Guangdong Provincial People's Hospital

Head of Pulmonary Surgery

Blood and Lymph Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Daunorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

study part 1 - dose daunorubicin standard dose daunorubicin in induction 1 (60 mg/m2) on days 3-5

study part 2: induction cycles double induction (only patients with good response)

study part 2: induction cycles single induction (only patients with good response)

standard induction dose of daunorubicin 60 mg/m2 on days 3-5

study part 1 - dose daunorubicin

single induction cycle versus double induction cycles (only patients with good response after first induction) Allocation is randomized for cytogenetic risk.

induction cycles

Christoph Röllig, Prof. Dr.

The proposed trial will address two clinically important questions for younger patients with newly diagnosed acute myeloid leukemia (AML): the optimal dose of daunorubicin in induction therapy and the necessity of a second induction cycle in patients with a good response after the first induction. The primary endpoint is the rate of good responders. Secondary outcomes will be relapse-free survival, overall survival and minimal residual disease kinetics. Patients will be recruited in about 40 treatment centers of the Study Alliance Leukemia study group over a period of 40 months. The results will be of great clinical relevance: First, the study could facilitate the establishment or confirmation of the optimal daunorubicin dose.

In the first part of the trial, patients will be randomly assigned to receive either 90 mg/m2 or 60 mg/m2 daunorubicin in the first induction cycle in addition to standard dosed cytarabine. Assuming a superiority of 90 mg/m2, 436 patients will be recruited. In the second part of the trial, good responders will be randomized to receive either a second or no further induction cycle. Assuming a non-inferiority of the single induction regarding the rate of complete remissions, a number of 360 patients will be included in the second part. Furthermore, in case of a non-inferiority of single versus double induction in good responders, about half of all younger AML patients could be spared a second induction cycle, leading to a reduction in treatment-related mortality, fewer days spent in hospital and improved quality of life.

As a result of the preplanned interim analysis of part I, the sponsor decided to suspend randomization in trial part I and to offer all patients the standard dose of 60 mg/m2 daunorubicin in both induction cycles (part I and II of the trial). Because of this an Amendment was sent to and approved by regulatories and ethics comitee.

The inclusion age was raised to 65 years based on the current German treatment guidelines in which patients up to the age of 65 are considered eligible for intensive induction chemotherapy with DA60 \[Onkopedia-Leitlinie 2017\].

Comparison Between Two Dose Levels of Daunorubicin and Between One vs. Two Induction Cycles for Adult Patients With AML

Randomized Comparison Between Two Dose Levels of Daunorubicin and Between One Versus Two Cycles of Induction Therapy for Adult Patients With Acute Myeloid Leukemia ≤65 Years

To investigate whether a higher dose of daunorubicin in induction chemotherapy leads to an increase in hematological good responders defined as having \<5% myeloid blasts on day 15 after start of induction therapy.

To investigate whether the rate of complete remissions (CR) after single induction is similar to that after double induction in patients with good response to induction I.

To investigate whether a higher dose of daunorubicin in induction chemotherapy will lead to an increase in cytogenetic and molecular complete remissions.

To investigate whether a higher dose of daunorubicin will lead to improved event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). To investigate whether EFS, RFS and OS are similar after single versus double induction in patients with good response to induction I.

To correlate the level of cytogenetic and molecular minimal residual disease after induction treatment with survival outcomes EFS, RFS and OS.

Rate of induction deaths (until day 60 or beginning of consolidation treatment - whichever occurs first)

Incidence of serious infectious complications Grades 3-4 (Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0

Sonographic cardiac left ventricular ejection fraction

Incidence of CTCAE grade ≥3 cardiac complications

University Hospital Dresden

Masaryk University

Technische Universität Dresden

Cytarabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

If WBC ≥ 30 G/L, chemotherapy the induction cycle :

* Daunorubicin 60 mg/m²/day IV on D1, D2, and D3
* Cytarabine 200 mg/m²/day D1 to D7
* OMEGAVEN® 2 ml/kg D1 to D9,

If WBC ≤ 30 G/L, OMEGAVEN during 48 hours

Induction cycle :

OMEGAVEN® 2 ml/kg D-2 to D7 Daunorubicin 60 mg/m²/day IV on D1, D2, and D3

- Cytarabine 200 mg/m²/day IV D1 to D7

bone marrow aspirate at D15: If BM blasts are \> 5% or if second induction course :

* Daunorubicin 35 mg/m²/day IV D17 and D18
* OMEGAVEN® 2 ml/kg
* Cytarabine 1000 mg/m²/12h IV on D17, D18, and D19

For all patients: G-CSF 5 µg/kg/day subcutaneously from D21 to hematopoietic recovery (PMN \> 1 G/L or \> 0.5 G/L during 3 days).

Consolidation will be administered at investigator's discretion

OMEGAVEN

Emmanuel GYAN, MD

Pilot study of the efficacy and tolerance of the adjunction of a Fish oil emulsion to daunorubicin and cytarabine chemotherapy for the treatment of Acute MYeloblastic Leukemia of Younger patients (under 61 years) with high-risk cytogenetics.

Adjunction of a Fish oil emulsion OMEGAVEN to daunorubicin and cytarabine chemotherapy for the treatment of Acute MYeloblastic Leukemia of Younger patients.

Pilot Study Efficacy and Tolerance Fish Oil Emulsion Daunorubicin and Cytarabine Treatment of AML Younger Patients

Pilot Study of the Efficacy and Tolerance of the Adjunction of a Fish Oil Emulsion to Daunorubicin and Cytarabine Chemotherapy for the Treatment of Acute MYeloblastic Leukemia of Younger Patients With High-risk Cytogenetics

Number of patients incomplete response rate after the adjunction of a Fish oil emulsion to daunorubicin and cytarabine chemotherapy for the induction of untreated AML

Number of patients with side effects during and after the admistration of a Fish oil emulsion with daunorubicin and cytarabine chemotherapy for the induction of untreated AML

Daily quantification of peripheral blasts by flow cytometry during the adjunction of a Fish oil emulsion to daunorubicin and cytarabine chemotherapy

Measure of plasma concentration of daunorubicin and cytarabine administered together with a fish oil emulsion

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Induction Lorlatinib in Stage III Non-small Cell Lung Cancer	NCT05740943	Stage III NSCLC Surgery	Lorlatinib	18 Years - 75 Years	Guangdong Provincial People's Hospital
Induction Lorlatinib in Stage III Non-small Cell Lung Cancer	NCT05740943	Stage III NSCLC Surgery	Lorlatinib	18 Years - 75 Years	Guangdong Provincial People's Hospital
Comparison Between Two Dose Levels of Daunorubicin and Between One vs. Two Induction Cycles for Adult Patients With AML	NCT02140242	Leukemia, Myelo...	study part 1 - ... induction cycle...	18 Years - 65 Years	Technische Universität Dresden
Comparison Between Two Dose Levels of Daunorubicin and Between One vs. Two Induction Cycles for Adult Patients With AML	NCT02140242	Leukemia, Myelo...	study part 1 - ... induction cycle...	18 Years - 65 Years	Technische Universität Dresden
Pilot Study Efficacy and Tolerance Fish Oil Emulsion Daunorubicin and Cytarabine Treatment of AML Younger Patients	NCT01999413	Acute Myeloid L...	OMEGAVEN Daunorubicin Cytarabine	18 Years - 61 Years	French Innovative Leukemia Organisation
Pilot Study Efficacy and Tolerance Fish Oil Emulsion Daunorubicin and Cytarabine Treatment of AML Younger Patients	NCT01999413	Acute Myeloid L...	OMEGAVEN Daunorubicin Cytarabine	18 Years - 61 Years	French Innovative Leukemia Organisation

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