Beschreibung

Efficacy of Carfilzomib in combination with Ibrutinib in Waldenström’s Macroglobulinemia (CZAR-1)

Studientherapie

Carfilzomib und Ibrutinib vs Ibrutinib alleine

Studienstatus

Rekrutierungsziel erreicht/keine neuen Patienten

Allgemeine Infos zum Antrag

Frau Nadine Röthling



nadine.roethling@uniklinik-ulm.de

Universitätsklinikum Ulm - Ulm (Institution, 12054)
Institut für Experimentelle Tumorforschung
Albert-Einstein-Allee 11
89081 Ulm

The primary objective of the trial is to test the efficacy and toxicity of Carfilzomib and Ibrutinib in patients with treatment naïve or relapsed WM.

male, female > 18 years

183

The aim of this study is to investigate the rate of CR or VGPR 12 months after the start of treatment using the response criteria updated at the Sixth IWWM8 (CR/VGPR).

• Response rate (CR, VGPR, PR, MR) and ORR 12 and 24 months after the start of treatment
• Best response
• Time to best response
• Time to first response
• Time to treatment failure
• Remission Duration
• Progression free survival
• Cause specific survival
• Overall survival
• Safety
• Quality of life

Spezifische Infos zum Antrag

• Proven clinicopathological diagnosis of WM
• De novo and relapsed/refractory WM independent of the genotype.
• Determination of mutational status of MYD88 and CXCR4.
• Patients must have at least one of the criteria to initiate treatment as partly defined by “Consensus Panel Two” recommendations from the Second International Workshop on Waldenström Macroglobulinemia
• World Health Organization (WHO)/ECOG performance status 0 to 2.
• Left ventricular ejection fraction e 40% as assessed by transthoracic echocardiogram (TTE).
o Age e than 18 years (male and female).
o Life expectancy > 3 months.
o Baseline platelet count e 50 x109/L , absolute neutrophil count e 0.75 x 109/L. (if not due to BM infiltration by the lymphoma).
o Meet the following pre-treatment laboratory criteria at the Screening visit conducted within 30 days prior to randomization:
§ ASAT (SGOT): < 3.0 times the ULN.
§ ALAT (SGPT): < 3.0 times the ULN.
§ Total Bilirubin: < 1.5 times the ULN, unless clearly related to the disease (except if due to Gilbert’s syndrome).
Serum creatinine: d 2 mg/dl.
• Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control for the duration of the therapy up to 6 months after end of therapy.
• Men must agree not to father a child for the duration of therapy and 6 months after (use of a condom) and must agree to advice a female partner to use a highly effective method of birth control.
• Voluntary written informed consent

• Previous treatments with Ibrutinib or BTK inhibitors, Carfilzomib)
• Serious medical or psychiatric illness (especially undergoing treatment) likely to interfere with participation in this clinical study.
• Uncontrolled bacterial, viral or fungal infection.
• Active HIV, HBV or HCV infection.
• Known interstitial lung disease.
• Central Nervous System involvement by lymphoma.
• History of a non-lymphoid malignancy (details see protocol)
• Uncontrolled illness (details see protocol)
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Primary amyloidosis.
• Recent major surgery within 30 days prior to randomization.
• Chemotherapy with approved or investigational anticancer therapeutic within 21 days prior to randomization.
• Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to randomization (i.e. prior radiation must have been to less than 30% of the bone marrow).
• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs.
• Infiltrative pulmonary disease, known pulmonary hypertension.
• Active infection within 14 days prior to randomization requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents. Such infection must be fully resolved prior to initiating study treatment.
• Pleural effusions requiring thoracentesis within 14 days prior to randomization.
• Ascites requiring paracentesis within 14 days prior to randomization.
• Uncontrolled hypertension, defined as an average systolic blood pressure > 159 mmHg or diastolic > 99 mmHg despite optimal treatment (measured following European Society of Hypertension/European Society of Cardiology [ESH/ESC] 2013 guidelines57.
• History of stroke or intracranial hemorrhage within 6 months prior to randomization
• Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal.
• Known severe persistent asthma within the past 2 years (see also https://www.nhlbi.nih.gov/files/docs/guidelines/asthsumm.pdf), or currently has uncontrolled asthma of any classification or at time of screening has an FEV1 of < 50% of predicted normal.
• Known cirrhosis.
• Autologous stem cell transplant less than 90 days prior to randomization.
• Allogeneic stem cell transplant less than 100 days prior to randomization.
• Vaccination with live attenuated vaccines within 30 days prior to randomization.
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or sponsor, if consulted, would pose a risk to subject safely or interfere with the study evaluation, procedures or completion.
• Women who are pregnant as well as women who are breast-feeding and do not consent to discontinue breast-feeding.
• Participation in another interventional clinical trial within 30 days before randomization in this study.

Carfilzomib 24 Monate
Ibrutinib bis Progress oder Unverträglichkeit (max. 10 Jahre innerhalb der Studie nach Einschluss erster Patient)

60 (international, in DE Zentrenzahl noch nicht festgelegt)

AMGEN (Finanzielle Unterstützung und Bereitstellung Carfilzomib)
JANSSEN (Bereitstellung Ibrutinib)

Ja

• Protokoll