Efficacy of first line Dexamethasone, Rituximab and Cyclophosphamide(DRC) +/- Bortezomib for patients with Waldenström's Macroglobulinemia

Phase 1

• Conditions: Waldenström's Macroglobulinemia; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-000506-37-CZ
• Lead Sponsor: niversity Hospital Ulm

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-07-18
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 384

Inclusion Criteria

A) Clinicopathological diagnosis of WM as defined by consensus panel
one of the Second International Workshop on WM. Pathological
diagnosis has to occur before study inclusion and randomization. In
addition, pathological specimens have to be sent to the national
pathological reference center at study inclusion and randomization. The
positivity for CD20 can be assumed from any previous bone marrow
immunohistochemistry or flow cytometry analysis performed up to 6
months prior to enrollment. Inclusion in the study will be based on
morphological and immunological criteria. Immunophenotyping will be
performed in each center and saved locally. Flow cytometry of bone marrow and blood cells will include at least one double staining and
assess the expression of the following antigens: surface
immunoglobulin, CD19, CD20, CD5, CD10 and CD23. Patients are eligible
if tumor cells express the following antigens: CD19, CD20, and if they are
negative for CD5, CD10 and CD23 expression. Patients with tumor cells
positive for CD5 and/or CD23 and morphologically similar to WM cells
may be included after ruling out other low-grade B-cell malignancies.
B) Patients must have at least one of the following critera to initiate
treatment as defined by Consensus Panel Two recommendations from
the Second International Workshop on Waldenström Macroglobulinemia.
a) Recurrent fever, night sweats, weight loss, fatigue
b) Hyperviscosity
c) Lympadenopathy which is either symptomatic or bulky (=5cm in
maximum diameter)
d) Symptomatic hepatomegaly and/or splenomegaly
e) Symptomatic organomegaly and/or organ or tissue infiltration
f) Peripheral neuropathy due to WM
g) Symptomatic cryoglobulinemia
h) Cold agglutinin anemia
i) IgM related immune hemolytic anemia and/or thrombocytopenia
j) Nephropathy related to WM
k) Amyloidosis related to WM
l) Hemoglobin =10g/dL
m) Platelet count <100x109/L
n) Serum monoclonal protein >5g/dL, even with no overt clinical
symptoms
C) Cumulative illness rating scale (CIRS) score less than 6 (see annex).
D) World Health Organization (WHO)/ECOG performance status 0 to 2.
E) Other criteria
a) Age = 18 years
b) Life expectancy >3 months.
c) Baseline platelet count =50x109/L (if not due to BM infiltration by the
lymphoma), absolute neutrophil count =0.75x109/L.
d) Meet the following pretreatment laboratory criteria at the Screening
visit conducted within 28 days of study enrollment:
- ASAT (SGOT): =3 times the upper limit of institutional laboratory
normal value
- ALAT (SGPT): =3 times the upper limit of institutional laboratory
normal value
- Total Bilirubin: =20 mg/L or 2 times the upper limit of institutional
laboratory normal value, unless clearly related to the disease (except if
due to Gilbert's syndrome)
- Serum creatinine = 2mg/dl
F) Premenopausal fertile females 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. A highly effective method of birth control is defined
as those which result in a low failure rate (i.e. less than 1% per year)
when used consistently and correctly such as implants, injectables,
combined oral contraceptives, some IUDs, sexual abstinence or
vasectomised partner.
G) Men must agree not to father a child for the duration of therapy and 6
months after and must agree to advice a female partner to use a highly
effective method of birth control.
H) Voluntary written informed consen

Exclusion Criteria

Prior systemic treatment of the WM (plasmapheresis and short – term
administration of corticosteroids < 4 weeks administered at a dose
equivalent to < 20 mg/day prednisone is allowed)
• Patient with hypersensitivity to dexamethasone.
• Serious medical or psychiatric illness 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
• Prior allergic reaction or severe anaphylactic reaction related to
humanized or murine monoclonal antibody.
• Central Nervous System involvement by lymphoma
• Prior history of malignancies unless the subject has been free of the
disease for = 5 years. Exceptions include the following:
- Basal cell carcinoma of the skin,
- Squamous cell carcinoma of the skin,
- Carcinoma in situ of the cervix,
- Carcinoma in situ of the breast,
- Incidental histologic finding of prostate cancer (TNM stage of T1a or
T1b).
• Uncontrolled illness including, but not limited to:
- Uncontrolled diabetes mellitus (as indicated
by metabolic derangements and/or severe diabetes mellitus related
uncontrolled organ complications)
- Chronic symptomatic congestive heart failure (Class NYHA III or IV).
- Unstable angina pectoris, angioplasty, stenting, or myocardial
infarction within 6 months
- Clinically significant cardiac arrhythmia that is symptomatic or requires
treatment, or asymptomatic sustained ventricular tachycardia.
- Known pericardial disease
• Subjects with = Grade 2 neuropathy.
• Women who are pregnant as well as women who are breast-feeding
and do not consent to discontinue breast-feeding.
• Participation in another clinical trial within 4 weeks before
randomization in this study
• No consent for registration, storage and processing of the individual
disease-characteristics and course as well as information of the family
physician about study participation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the trial is to evaluate whether the addition of<br>Bortezomib to the combination regimen<br>Dexamethasone/Rituximab/Cyclophosphamide (B-DRC) improves PFS<br>compared to DRC alone.;Secondary Objective: To compare the efficacy and safety of bortezomib in combination with<br>DRC using other parameters of efficacy:<br>- Response rates (CR, VGPR, PR, MR) and overall response (ORR) four<br>weeks after the end of induction therapy<br>- Best response<br>- Time to best response<br>- Time to first response<br>- Time to treatment failure<br>- Remission Duration<br>- Cause specific survival<br>- Overall survival<br>- Cause specific survival<br>- Overall survival;Primary end point(s): The primary end point of the trial is progression-free survival (PFS).