Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Acalabrutinib

After 18 months of acalabrutinib treatment, patients will stop acalabrutinib treatment for watch and monitor until month 60. If progression disease, patients will be re-treated with ACA at the last received dose after central reviewing of treatment criteria.

After 18 months of acalabrutinib treatment, patients will continue acalabrutinib treatment until month 60. If progression disease or unacceptable toxicity, patients will receive next line therapy at the discretion of their physicians and according to iwCLL 2018 criteria

discontinuation of acalabrutinib after 18 months in treatment-naïve CLL patients

Stop ACA

continuation of acalabrutinib at the same dose

ACA Continuation

Delphine NOLLET

Valérie ROUILLE, Pr

Aline CLAVERT, MD

Driss CHAOUI

Safia CHEBREK, Dr

Julie GAY, MD

Vincent LEVY, Pr

Xavier CAHU, Dr

Romain GUIEZE, Dr

Laurence SIMON, Dr

Lysiane MOLINA, Dr

Kamel LARIBI, Dr

Bénédicte HIVERT, Dr

Anne-Sophie MICHALLET, Dr

Thérèse AURRAN, Dr

Philippe CARASSOU, MD

Emanuelle TCHERNONOG, Dr

Bernard DRENOU, Dr

Marlene OCHMANN, Dr

Damien ROOS WEIL, Dr

Laurence SANHES, Dr

Marie-Sarah DILHUYDY, MD

Emmanuelle FERRANT, MD

Cécile TOMOWIAK, Dr

Hugo Gonzalez, Dr

Anne QUINQUENEL, Dr

Sophie DE GUIBERT, Pr

Stéphane LEPRETRE, Pr

Emilie CHALAYER, Dr

Loïc YSEBAERT, Dr

Caroline DARTIGEAS, Dr

Pierre FEUGIER, Pr

Antoine BONNET, Dr

Fatiha MERABET, Dr

Loïc Ysebaert, Pr

Romain GUIEZE, Pr

The irreversible Bruton's Tyrosine Kinase (BTK) inhibitor acalabrutinib (ACA) has potent clinical activity as a single agent in patients with treatment naive and Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL).

However, a growing body of concerns is raising regarding the unlimited administration of targeted therapy as BTKi. First, long-term treatments expose the patients to increased risk of specific adverse events (infections, bleeding events or cardiovascular problems). Second, continuous administration might also increase the risk of clonal evolution and therapeutic resistance resulting from genetic alterations such as BTK or PLCG2 mutations. Discontinuation of therapy after a fixed period is expected to prevent these events.

Rapid and deep responses yielded by ACA in elderly patients pave the way of investigating a limited 18-months period schedule. This study aims to investigate the 1-year PFS upon ACA discontinuation and efficacy of restarting ACA upon symptomatic relapse.

This multicenter, non comparative, randomized phase II trial aims at evaluating the impact of a stopping ACA strategy on PFS of CLL patients \>70 years or with coexisting comorbidities.

Patients will receive continuous Acalabrutinib (ACA) at 100 mg bid for 18 months. Dose adaptations will be made according to labels.

In case of first occurrence of grade ≥3 non-hematological toxicity, febrile grade ≥3 neutropenia or grade ≥4 hematological toxicity treatment must be stopped until recovering grade 1 or baseline state.

* 1st and second occurrence : restart at 100 mg twice daily
* 3rd occurrence : restart at 100 mg once daily
* 4th occurrence : discontinue acalabrutinib

At month 19 day 1, patients will be randomized (1:2) in two arms:

* Arm 1 = Control arm (acalabrutinib) continuing acalabrutinib until disease progression or unacceptable toxicity or
* Arm 2 = Experimental arm (watch and monitor) without ACA (see trial design).

Upon progression in the experimental arm, all patients will be re-treated with ACA at the last received dose after central reviewing of treatment criteria.

Upon progression in the control arm, patients will receive next line therapy at the discretion of their physicians and according to iwCLL 2018 criteria.

Patients will be monitored every three months until M31 then every 6 months until M60 or progression for both response and toxicity according to CTCAE v.5.

Minimal/Measurable Residual Disease (MRD) assessment will be done at month 19 day 1 in the peripheral blood.

CT-scan will be performed at baseline, then at month 19 day 1 and every 6 months within the year after randomization.

multicenter, non comparative, randomized, stop and restart

STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia

Time from randomization (M19 : discontinuation of acalabrutinib after of 18 months treatment) to progression (needing therapy or not) or death from any cause

French Innovative Leukemia Organisation

Disease Progression

Antirheumatic Agents

Amino Acids

Rituximab

Chlorambucil

Antineoplastic Agents, Immunological

Immunologic Factors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tyrosine

Acalabrutinib will be orally administered until disease progression or unacceptable toxicity

Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles

Rituximab: 375 mg/m2 IV infusion on Day 1 of Cycle 1. 500 mg/m2 IV infusion on Day 1 for each of subsequent cycles (Cycles 2-6)

Chlorambucil: 0.5 mg/kg body weight orally on Day 1 and Day 15 of Cycles 1-6

Lugui Qiu, MD

This is a randomized, multicenter, open-label, Phase 3 study to evaluate the efficacy and safety of Acalabrutinib versus Chlorambucil plus Rituximab in subjects with Previously Untreated Chronic Lymphocytic Leukemia.

Patients be randomized in a 1:1 ratio into 2 arms to receive either acalabrutinib monotherapy (Arm A) or rituximab in combination with chlorambucil (Arm B). The primary objective of this study is to compare the efficacy of acalabrutinib relative to chlorambucil plus rituximab in subjects with previously untreated chronic lymphocytic leukemia without del(17p) or TP53 mutation.

Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia

A Randomized, Multicenter, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of Acalabrutinib Versus Chlorambucil Plus Rituximab in Subjects With Previously Untreated Chronic Lymphocytic Leukemia

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Progression free survival is defined as time from randomization until progression or death due to any cause (whichever occurs first)

AstraZeneca

Nutritional and Metabolic Diseases

Lymphoma

Vitamin D Deficiency

Lymphoma, Non-Hodgkin

Avitaminosis

Deficiency Diseases

Malnutrition

Nutrition Disorders

Lymphosarcoma

Micronutrients

Bone Density Conservation Agents

Vitamins

Vitamin D

Cholecalciferol

Trientine

Trace Elements

Hormones

Calcium

Calcium, Dietary

Vitamin D3

Calciferol

Patients receive high-dose cholecalciferol PO daily for 3 years in the absence of disease progression or unacceptable toxicity.

Patients receive low-dose cholecalciferol PO daily for 3 years in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Julie M Vose, MD, MBA

This randomized pilot early phase I trial studies how well cholecalciferol works in treating patients with newly diagnosed non-Hodgkin lymphoma or chronic lymphocytic leukemia with low levels of vitamin D (vitamin D deficiency). Cholecalciferol may increase levels of vitamin D and improve survival in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia receiving standard of care chemotherapy.

PRIMARY OBJECTIVES:

I. To evaluate the 3 year progression-free survival (PFS), defined as time from the time of study entry of watch and wait or newly diagnosed non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) until relapse, progression, or death from any cause.

SECONDARY OBJECTIVES:

I. To evaluate changes in the levels of serum vitamin D levels during therapy with daily oral vitamin D supplementation (cholecalciferol).

II. To evaluate the overall survival (OS), defined as time from the time of study entry of watch and wait patients or newly diagnosed NHL or CLL until death from any cause.

OUTLINE: Patients with low levels of vitamin D are randomized to 1 of 2 arms and patients with normal levels are assigned to Arm III.

ARM I: Patients receive high-dose cholecalciferol orally (PO) daily for 3 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive low-dose cholecalciferol PO daily for 3 years in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive no intervention.

Cholecalciferol in Newly Diagnosed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia With Vitamin D Deficiency

A Pilot Study of Vitamin D Replacement in Patients With Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia With Low Vitamin D Levels

The 3-year progression-free survival will be presented using Kaplan-Meier curves and will be presented for the normal serum vitamin D control group and the low and high dose randomized groups. Each randomized group (low and high dose) will be compared to a historical fixed expected 3-year progression-free survival of 45% using a one-sample logrank test following the method of Woolson (1981).

Will be described for the low dose and high dose groups and compared between groups using a Chi-square. The frequency of occurrence of overall toxicity, categorized by toxicity grades, will be described for the low dose and high dose groups and compared between groups using a Chi-square.

The 3-year overall survival will be presented using Kaplan-Meier curves and will be presented for the normal serum vitamin D control group and the low and high dose randomized groups. Each randomized group (low and high dose) will be compared to a historical fixed expected 3-year overall survival of 80% using a one-sample logrank test following the method of Woolson (1981).

National Cancer Institute (NCI)

University of Nebraska

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia	NCT04963946	Untreated Chron...	Stop ACA ACA Continuatio...	70 Years -	French Innovative Leukemia Organisation
Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia	NCT04075292	Untreated Chron...	Acalabrutinib Rituximab Chlorambucil	18 Years - 130 Years	AstraZeneca
Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia	NCT04075292	Untreated Chron...	Acalabrutinib Rituximab Chlorambucil	18 Years - 130 Years	AstraZeneca
Cholecalciferol in Newly Diagnosed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia With Vitamin D Deficiency	NCT02553447	Chronic Lymphoc... Non-Hodgkin Lym... Untreated Chron... Vitamin D Defic...	Cholecalciferol Laboratory Biom...	19 Years -	University of Nebraska

Spots Global Cancer Trial Database for untreated chronic lymphocytic leukemia