Study to evaluate the effects of CLR 131 in patients with B-Cell malignancies (CLOVER-1) and expansion study to evaluate the effects of CLR 131 specifically in patients with Waldenstrom Macroglobulinemia (CLOVER-WaM)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cellectar Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Dec 2021 → ongoing

Decision date (initial)

2024-07-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Cellectar Biosciences, Inc.

External identifiers

EU CT number

2023-508671-37-00

EudraCT number

2020-005297-10

WHO UTN

U1111-1297-7868

ClinicalTrials.gov

NCT02952508

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of the study is to determine the major response rate (MRR) of CLR 131 in patients with WM who have received at least two prior lines of therapy.

Secondary objectives 2

1. 1. 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
2. 2. To further describe the safety and tolerability (AE) profile of CLR 131 in the population under study, and in sub-populations

Conditions and MedDRA coding

Waldenstrom Macroglobulinemia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002745-PIP02-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Histologically or cytologically confirmed WM. Patients with a diagnosis of LPL may be enrolled with prior Sponsor approval.
2. 2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
3. 3. Patient is 18 years of age or older.
4. 4. Life expectancy of at least 6 months.
5. 5. Received at least two prior lines of therapy for WM.

Exclusion criteria 10

1. 1. Ongoing Grade 2 or greater toxicities due to previous therapies, excluding alopecia.
2. 2. Prior external-beam RT resulting in greater than 20% of total bone marrow receiving greater than 20 Gy.
3. 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. 4. Patients with second malignancies in addition to WM, if the second malignancy has required systemic therapy in the last 2 years. Exceptions to this criterion include secondary malignancies in remission, successfully treated skin malignancies, skin malignancies only requiring topic treatment or surgical excision, or other cancer that do not require therapy.
5. 5. Anti-cancer therapy within two weeks of initial CLR 131 infusion.
6. 6. Major surgery within 6 weeks of enrollment.
7. 7. History of hypersensitivity to thyroid protection medication (e.g., potassium iodide, Lugol’s solution, etc.)
8. 8. Known history of human immunodeficiency virus, active or chronic hepatitis C, or hepatitis B infection.
9. 9. 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.
10. 10. Pregnancy or breast-feeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 at least two prior lines of therapy.

Secondary endpoints 5

1. 1. Overall response rate (ORR), defined as the proportion of patients with a MR, PR, VGPR, or CR determined from criteria modified from the VIth Waldenstrom’s Macroglobulinemia Criteria for Response Assessment.
2. 2. Treatment free survival (TFS), defined as the time from last CLR 131 dose to time to initiation of subsequent therapy or death.
3. 3. Duration of response (DOR) is defined as the time from the first documentation of response (including CR, VGPR, PR) to PD or death. For DOR, patients who are alive and progression free during this study will have their event time censored on the last disease assessment.
4. 4. Clinical benefit rate (CBR) 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.
5. 5. Safety. Adverse events (AEs), serious AE (SAEs), AEs with Grade ≥ 3, laboratory results, vital signs, electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status (PS).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cellectar Biosciences Inc.

Sponsor organisation

Cellectar Biosciences Inc.

Address

100 Campus Drive

City

Florham Park

Postcode

07932-1020

Country

United States

Scientific contact point

Organisation

Cellectar Biosciences Inc.

Contact name

Clinical Trial Team

Public contact point

Organisation

Cellectar Biosciences Inc.

Contact name

Clinical Trial Team

Third parties 5

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications