E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The hematologic disease known as Waldenstrom’s Macroglobulinemia (WM). WM is a type of Lymphoplasmacytic lymphoma (LPL), a rare and chronic form of B-cell non-Hodgkin lymphoma (NHL), characterized by small B lymphocytes, plasmacytoid lymphocytes, and plasma cells typically involving the bone marrow, lymph nodes, and spleen. |
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E.1.1.1 | Medical condition in easily understood language |
Waldenstrom’s Macroglobulinemia is a specific type of cancer that form in certain blood cells known as B-cells. B-cells are part of the immune system. These cancers are very difficult to treat. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054695 |
E.1.2 | Term | Waldenstrom's macroglobulinemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to determine the major response rate (MRR) of CLR 131 in patients with WM who have received first line standard of care and had a sub-optimal response or have failed treatment with a Bruton's tyrosine kinase (BTK) inhibitor. |
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E.2.2 | Secondary objectives of the trial |
• To determine the overall response rate (ORR), treatment free survival (TFS), duration of response (DOR), and clinical benefit rate (CBR) in the population under study • To further describe the safety and tolerability profile of CLR 131 in the population under study |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed WM. Patients with a diagnosis of LPL may be enrolled with prior Sponsor approval. 2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2. 3. Patient is 18 years of age or older. 4. Life expectancy of at least 6 months. 5. Received first line standard of care. 6. Achieve a sub-optimal response to or failed treatment with a BTK inhibitor.
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E.4 | Principal exclusion criteria |
1. Ongoing Grade 2 or greater toxicities due to previous therapies, excluding alopecia (subject to the additional laboratory abnormalities listed below). However, stable, tolerable Grade 2 AEs (e.g., neuropathy) and gastrointestinal AEs (e.g., nausea) persistent after adequate management may be allowed after discussion with the Medical Monitor. 2. Prior external-beam RT resulting in greater than 20% of total bone marrow receiving greater than 20 Gy. 3. Prior total body or hemi-body irradiation. Patients who have received prior low-dose total body or hemi-body irradiation may be allowed on a case-by-case basis after discussion with Sponsor (considerations may include factors such as time since irradiation, total lifetime accumulated dose, etc.). 4. Patients with second malignancies in addition to WM, if the second malignancy has required therapy in the last 2 years or is not in remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. 5. Anti-cancer therapy within two weeks of initial CLR 131 infusion. 6. Radiation therapy, chemotherapy, immunotherapy within 2 weeks, and investigational therapy within 5 half-lives of eligibility-defining bone marrow biopsy. 7. Major surgery within 6 weeks of enrollment. 8. History of hypersensitivity to thyroid protection medication (e.g., potassium iodide, Lugol’s solution, etc.). 9. Known history of human immunodeficiency virus, hepatitis C, or hepatitis B infection. 10. Presence of active infection within 72 hours prior to dosing; patients with ongoing use of prophylactic antibiotics, antifungals, or antivirals are eligible as long as there is no evidence of active infection and the antibiotics, antifungals, or antivirals are not included on the list of prohibited medications. 11. Pregnancy or breast-feeding.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the MRR, which is defined as the proportion of patients following the infusion of CLR 131 with complete response (CR), very good partial response (VGPR), or partial response (PR) determined from criteria modified from the VIth Waldenstrom’s Macroglobulinemia Criteria for Response Assessment up to 12 months post first CLR 131 infusion in WM patients who have received first line standard of care and have had a sub-optimal response to or failed treatment with a BTK inhibitor. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 8, 15, 22, 29, 36, 43, 50, 57 Month 6 post first CLR 131 infusion year 1 post first CLR 131 infusion
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints include ORR, TFS, DOR, CBR, and safety. Overall response rate is defined as the proportion of patients with a minor response (MR), PR, VGPR, or CR determined from criteria modified from the VIth Waldenstrom’s Macroglobulinemia Criteria for Response Assessment. Treatment free survival is defined as the time from last CLR 131 dose to time to initiation of subsequent therapy or death. Duration of response is defined as the time from the first documentation of response (including CR, VGPR, PR) to progressive disease (PD) or death. Clinical benefit rate is defined as the proportion of patients with CR, VGPR, PR, MR, and SD determined from criteria modified from the VIth Waldenstrom’s Macroglobulinemia Criteria for Response Assessment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1, 8, 15, 22, 29, 36, 43, 50 and 57 Month 6 post first CLR 131 infusion year 1 post first CLR 131 infusion AE/SAE profile is evaluated at all visits |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Israel |
United States |
France |
Greece |
Italy |
Spain |
United Kingdom |
Czechia |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Patients will be assessed for approximately 3 years post initial CLR 131 dosing. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |