Main info

Identificatie:

HO124 WM

Sponsor:

HOVON

Working group party:

Lymphoma

Age:

>= 18

Stadium:

2de lijn

Echelon:

Level B

Included patients:

60

(of 72)

Active sites:

21

(of 22)

Title:

HOVON 124 WM/ECWM-R2 study: A prospective phase I/II trial of the combination of ixazomib citrate, rituximab and dexamethasone in patients with relapsed or progressive Waldenström’s macroglobulinemia. A HOVON/Greek Myeloma Study Group study.

Timeline

News

Flow

Details

Phase:

Prospective Phase I/II study

Monitoring Type:

Not any more

Objectives:

Phase I part:

• Establish maximum tolerated dose for the combination of ixazomib citrate and dexamethasone

Phase II part:

• Assess the efficacy of oral ixazomib citrate in combination with rituximab and dexamethasone

Eligibility

Inclusion Criteria:

• A diagnosis of WM (lymphoplasmacytoid lymphoma in the bone marrow with an IgM M-protein)
• Age ≥ 18 years
• WHO 0-2
• Presence of an IgM M-protein in the serum (as demonstrated by SPEP and IF)
• Measurable disease (IgM M-protein > 10 g/l (1 g/dl or, in case the M-protein is present but unquantifiable, total serum IgM level > 10 g/l (1 g/dl))
• Symptomatic disease
• ≥ 1 prior lines of treatment
• Patients showing progressive disease under treatment with chemotherapy only (e.g. chlorambucil, CVP, fludarabine or fludarabine/cyclophosphamide) are allowed on study
• Platelets > 75x109/l. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
• ANC >1.0 x109/l
• Negative pregnancy test at study entry for women of childbearing potential
• A female patient is either post-menopausal for at least 1 year before the screening visit, or surgically sterile, or, if of childbearing potential, agrees to practice 2 effective methods of contraception at the same time, from the time of signing the informed consent until 12 months after the last dose of rituximab, or agrees to completely abstain from heterosexual intercourse. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception)
• Male patients, even if surgically sterilized, (i.e., status post vasectomy) must agree to practice effective barrier contraception during the entire study period and through 90 days after the last dose of ixazomib and/or rituximab, or agree to completely abstain from heterosexual intercourse. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception)
• Written informed consent
• Prior plasmapheresis in case of symptomatic hyperviscosity is allowed

Exclusion Criteria:

• Bortezomib refractory (no PR/CR after treatment with bortezomib, and/or progression within 6 months of treatment with bortezomib)
• Rituximab refractory (progressive disease during treatment or within 6 months after last administration of rituximab)
• WHO performance status >2
• Amyloidosis
• Peripheral neuropathy, grade 3 or higher
• Creatinine clearance <30 ml/min
• Known HIV seropositivity
• Patients with active hepatitis B or C infection
• Known intolerance of rituximab and/or boron
• Bing Neel syndrome or other severe neurological disorders
• Severe cardiac dysfunction (NYHA classification III-IV; see appendix….)
• Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix …)
• Significant hepatic dysfunction (defined as total bilirubin >1.5 ULN (unless caused by Gilbert syndrome) and/or transaminases ≥3 times upper limit of normal, unless caused by WM
• Active, uncontrolled infections
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, hypertension, cancer)
• A history of other malignancies, unless the malignancy has been in remission for at least 5 years (with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma)
• Pregnancy or breastfeeding
• Current participation in another clinical trial
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals