A randomized phase II study for the evaluation of T cell depleted non-myeloablative allogeneic stem cell transplantation followed by early consolidation with lenalidomide or lenalidomide combined with bortezomib and subsequent DLI for patients with multiple myeloma in progression or relapse following first line therapy

Phase 2

Completed

• Conditions: Kahlers disease; Multiple Myeloma; 10035227

• Registration Number: NL-OMON36688
• Lead Sponsor: HOVO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 110

Inclusion Criteria

- Patients with multiple myeloma with a first relapse or progression after first line therapy;
- Relapsed or progressive patients have received reinduction therapy before entering this trial;
- At least PR after reinduction treatment;
- 18-65 years,inclusive
- HLA-identical sibling or unrelated donor completely matched (10/10) (excluding identical
twins);
- WHO-performance status 0-2;
- Written informed consent

Exclusion Criteria

- No previous Allo-SCT;
- Severe pulmonary dysfunction (CTCAE grade III-IV, see protocol appendix D );
- Severe neurological or psychiatric disease;
- Patients with neuropathy, CTC grade 3 or higher;
- Significant hepatic dysfunction (serum bilirubin or transaminases * 3 times upper limit of
normal);
- Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration);
- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes,
infection, hypertension, cancer, etc.);
- History of active malignancy during the past 5 years with the exception of basal carcinoma of
the skin or or carcinoma *in situ* of the cervix or breast;
- Patient known to be HIV-positive;
- Patients with brain disease with the exception of those patients whose brain disease has
been treated with either radiotherapy or surgery and remains asymptomatic, with no active
brain disease, as shown by CT scan or MRI, for at least 6 months;
- The development of erythema nodosum if characterized by a desquamating rash while taking
thalidomide, lenalidomide or borium;
- Pregnant or breast-feeding female patients. Negative pregnancy test at study is mandatory
for female patients of childbearing potential;
- Not able and not willing to use adequate contraception during therapy;
- Any psychological, familial, sociological and geographical condition potentially hampering
compliance with the study protocol and follow-up schedule;
- Severe cardiac dysfunction (NYHA classification II-IV, see protocol appendix E).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Failure free duration (FFD) at 9 months post-transplant. Patients count as a<br /><br>failure (= event) at the earliest time point within 9 months after Allo-SCT at<br /><br>which any of the following events occurs:<br /><br>- Onset of acute GvHD grade 3-4 without prior DLI;<br /><br>- Onset of extensive chronic GvHD without prior DLI;<br /><br>- Non-hematological toxicity CTCAE grade 4;<br /><br>- Systemic therapy for uncontrolled myeloma other than the assigned study<br /><br>treatment of lenalidomide or lenalidomide/bortezomib and DLI<br /><br>- Death not due to (progression of) MM, which is in fact TRM.<br /><br>Patients without a failure within 9 months post Allo-SCT will be censored at 9<br /><br>months, at the date of progression, or when they go off protocol treatment,<br /><br>whichever comes first.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Toxicity profile and compliance related to each treatment step and intervals<br /><br>between treatment steps (Allo-SCT, consolidation chemotherapy as well as<br /><br>pre-emptive DLI);<br /><br>- Percentage of patients with a 1st pre-emptive DLI within 6-9 months from the<br /><br>date of Allo-SCT;<br /><br>- Response, improvement of response and conversion to full donor chimerism<br /><br>during the separate treatment phases (i.e. from Allo-SCT until consolidation;<br /><br>from consolidation to DLI; and after DLI);<br /><br>- CR rate<br /><br>- Progression-free survival (PFS; i.e. time from registration until<br /><br>progression, relapse or death, whichever comes first);<br /><br>- PFS from Allo-SCT;<br /><br>- Overall survival (OS) measured from time of registration;<br /><br>- OS from Allo-SCT;<br /><br>- The poportion of patients that complete 1, 2 resp. 3 induction cycles;<br /><br>- Quality of life as defined by the EORTC QLQ-C30 and QLQ-MY20.</p><br>