Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02952508




Registration number
NCT02952508
Ethics application status
Date submitted
28/10/2016
Date registered
2/11/2016
Date last updated
6/06/2024

Titles & IDs
Public title
Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia
Scientific title
An Open-Label, Multicenter, Phase 2 Study of Iopofosine I 131 (CLR 131) in Patients With Relapsed or Refractory (R/R) Select B-Cell Malignancies (CLOVER-1) and Expansion Cohort in Patients With Waldenstrom Macroglobulinemia (CLOVER-WaM)
Secondary ID [1] 0 0
DCL-16-001
Universal Trial Number (UTN)
Trial acronym
CLOVER-WaM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Waldenstrom Macroglobulinemia 0 0
Multiple Myeloma 0 0
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Lymphoplasmacytic Lymphoma 0 0
Marginal Zone Lymphoma 0 0
Mantle Cell Lymphoma 0 0
Diffuse Large B Cell Lymphoma 0 0
Central Nervous System Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Iopofosine I 131 single dose
Treatment: Drugs - Iopofosine I 131 multiple dose
Treatment: Drugs - Iopofosine I 131 fractionated dose

Experimental: Iopofosine I 131, intravenous administration WM - Iopofosine I 131 in Waldenstroms Macroglobulinemia

Experimental: Iopofosine I 131, intravenous administration MM - Iopofosine I 131 in Multiple Myeloma

Experimental: Iopofosine I 131, intravenous administration CNS Lymphoma - Iopofosine I 131 in Central Nervous System Lymphoma

Experimental: Iopofosine I 131 intravenous administration NHL [CLOSED] - Iopofosine I 131 in Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, and Diffuse Large B-Cell Lymphoma


Treatment: Drugs: Iopofosine I 131 single dose
Radiopharmaceutical

Treatment: Drugs: Iopofosine I 131 multiple dose
Radiopharmaceutical

Treatment: Drugs: Iopofosine I 131 fractionated dose
Radiopharmaceutical
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A [CLOVER-1] Clinical benefit rate
Timepoint [1] 0 0
84 days
Primary outcome [2] 0 0
Part B [CLOVER-WaM] Major Response Rate
Timepoint [2] 0 0
12 months
Secondary outcome [1] 0 0
Part A [CLOVER-1] Overall Response Rate
Timepoint [1] 0 0
135 days
Secondary outcome [2] 0 0
Part A [CLOVER-1] Progression Free Survival
Timepoint [2] 0 0
135 days
Secondary outcome [3] 0 0
Part A [CLOVER-1] Time to Next Treatment
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Part A [CLOVER-1] Overall Survival
Timepoint [4] 0 0
135 days
Secondary outcome [5] 0 0
Part A [CLOVER-1] Duration of Response
Timepoint [5] 0 0
135 days
Secondary outcome [6] 0 0
Part B [CLOVER-WaM] Overall Response Rate
Timepoint [6] 0 0
135 days
Secondary outcome [7] 0 0
Part B [CLOVER-WaM] Treatment Free Survival
Timepoint [7] 0 0
135 days
Secondary outcome [8] 0 0
Part B [CLOVER-WaM] Duration of Response
Timepoint [8] 0 0
135 days
Secondary outcome [9] 0 0
Part B [CLOVER-WaM] Clinical Benefit Rate
Timepoint [9] 0 0
135 days

Eligibility
Key inclusion criteria
[CLOVER-1] All Patients

- Histologically or cytologically confirmed MM; Patients with primary or secondary CNSL
may be enrolled.

- ECOG performance status of 0 to 2

- 18 years of age or older

- Life expectancy of at least 6 months

- Platelets = 75,000/µL (if full-dose anticoagulation therapy is used, platelets =
100,000/µL are required)

- WBC count = 3000/µL

- Absolute neutrophil count = 1500/µL

- Hemoglobin = 9 g/dL (last transfusion, if any, must be at least 1 week prior to study
registration, and no transfusions are allowed between registration and dosing)

- Estimated glomerular filtration rate = 30 mL/min/1.73 m2

- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 2.5 × upper
limit of normal (ULN)

- Bilirubin < 1.5 × ULN

- International normalized ratio (INR) < 2.5

- If patient is on full-dose anticoagulation therapy, the anticoagulation therapy must
be reversible and reversal of the anticoagulation therapy must not be
life-threatening, as judged by the Investigator

- Patients who have undergone stem cell transplant must be at least 100 days from
transplant

Patients with Multiple Myeloma

- At least 5 prior regimens, which must include at least 1 approved proteasome inhibitor
(bortezomib, carfilzomib, or ixazomib), at least 1 approved immunomodulatory agent
(thalidomide, lenalidomide, or pomalidomide), and at least 1 approved monoclonal
antibody (e.g., daratumumab or elotuzumab) with or without maintenance therapy, unless
patients are intolerable to such agents or ineligible to receive such agents.

- At least triple-class refractory (refractory to a proteasome inhibitor,
immunomodulatory agent, and a monoclonal antibody)

- Progressive disease defined by any of the following:

- 25% increase in serum M-protein from the lowest response value during (or after)
last therapy and/or absolute increase in serum M-protein of = 0.5 g/dL

- 25% increase in urine M-protein from the lowest response value during (or after)
last therapy and/or absolute increase in urine M-protein of = 200 mg/24 h

- 25% increase in bone marrow plasma cell percentage from the lowest response value
during (or after) last therapy. Absolute bone marrow plasma cell percentage must
be = 10% unless prior CR when absolute bone marrow plasma cell percentage must be
= 5%.

- 25% increase in serum FLC level from the lowest response value during (or after)
last therapy; the absolute increase must be > 10 mg/dL

- New onset hypercalcemia > 11.5 mg/dL

- Failure to obtain a partial response or better to current treatment, or cannot
further improve their response to current treatment

- Appearance of new extramedullary disease

- Measurable disease defined by any of the following:

- Serum M-protein > 0.5 g/dL

- Urine M-protein > 200 mg/24 h

- Serum FLC assay: Involved FLC level = 10 mg/dL provided serum FLC ratio is
abnormal.

[CLOSED] Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma,
Lymphoplasmacytic Lymphoma/Waldenstom Macroglobulinemia, or Marginal Zone Lymphoma

- Prior treatment with at least 2 prior regimens, which may include chemotherapy, an
approved anti-CD20 antibody with or without maintenance therapy, and an approved
targeted agent, unless patients are ineligible to receive such agents

- Patients with Helicobacter pylori+ mucosa-associated lymphoid tissue lymphoma must
have received 1 prior antibiotic regimen for H pylori

- At least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable
extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. Additional
parameters (e.g., measurable IgM for patients with Lymphoplasmacytic Lymphoma) may be
allowed if they meet current NCCN guidelines for symptomatic disease. Patients with
uptake by FDG-PET scan may be allowed with prior approval of Sponsor.

[CLOSED] Patients with Mantle Cell Lymphoma

- Prior treatment with at least 1 prior regimen

- At least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable
extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. Patients with
uptake by FDG-PET scan may be allowed with prior approval of Sponsor.

[CLOSED] Patients with Diffuse Large B-Cell Lymphoma

- Relapsed or refractory to combination chemotherapy for DLBCL that contains rituximab
and an anthracycline; or is intolerable to such agents. Relapsed disease is defined as
either recurrence of disease after a CR or PD after achieving a partial response (PR)
or SD. Refractory disease is defined as failure to achieve at least SD with any 1 line
of therapy or with PD = 3 months of the most recent chemotherapy regimen.

- At least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable
extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. Patients with
uptake by FDG-PET scan may be allowed with prior approval of Sponsor.

Patients with CNS Lymphoma

- Must have biopsy-proven disease and must have received at least one prior intervention
for their disease.

- Must be at least two weeks from CNS biopsy before administration of iopofosine I 131.

- Must have at least one lesion with enhancement on brain imaging.

- Stable (or decreasing) dose of corticosteroids or anti-convulsant medication for at
least 7 days prior to dosing

[CLOVER-1]
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Ongoing Grade 2 or greater toxicities due to previous therapies. Stable, tolerable
Grade 2 AEs (eg, neuropathy) may be allowed.

- Prior external-beam RT resulting in greater than 20% of total bone marrow receiving
greater than 20 Gy.

- 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.)

- Extradural tumor in contact with the spinal cord or tumor located where swelling in
response to therapy may impinge upon the spinal cord

- For patients with CLL/SLL, LPL, or MZL, transformation to a more aggressive form of
NHL

- Ongoing chronic immunosuppressive therapy

- Clinically significant bleeding event within prior 6 months

- Ongoing anti-platelet therapy (except low-dose aspirin [eg, 81 mg daily] for
cardioprotection)

- Anti-cancer therapy within two weeks of initial iopofosine I 131 infusion. Low dose
dexamethasone for symptom management is allowed

- Radiation therapy, chemotherapy, immunotherapy, or investigational therapy within 2
weeks of eligibility-defining bone marrow biopsy.

- For patients with primary or secondary CNSL, active bleeding in the tumor bed and/or
uncontrolled seizure activity

[CLOVER-WaM] Inclusion Criteria

- Histologically or cytologically confirmed WM. Patients with a diagnosis of LPL may be
enrolled with prior Sponsor approval.

- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0
to 2 (Appendix C)

- Patient is 18 years of age or older

- Life expectancy of at least 6 months

- Received at least two prior lines of therapy for WM

- Measurable IgM (above upper limit of normal) OR at least one measurable nodal lesion
with longest diameter > 15 mm or one measurable extranodal lesion (e.g., hepatic
nodule) with longest diameter > 10 mm

[CLOVER-WaM] Exclusion Criteria

- Ongoing Grade 2 or greater toxicities due to previous therapies, excluding alopecia.

- Prior external-beam RT resulting in greater than 20% of total bone marrow receiving
greater than 20 Gy.

- 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.)

- 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

- Anti-cancer therapy within two weeks of initial iopofosine I 131 infusion.

- Need for acute treatment of WM (e.g., those with hyperviscosity)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/07/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Cellectar Biosciences site - Concord
Recruitment hospital [2] 0 0
Cellectar Biosciences - Adelaide
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Brazil
State/province [19] 0 0
Bahia
Country [20] 0 0
Brazil
State/province [20] 0 0
Parana
Country [21] 0 0
Brazil
State/province [21] 0 0
RioGrande Do Sul
Country [22] 0 0
Brazil
State/province [22] 0 0
Santa Catarina
Country [23] 0 0
Czechia
State/province [23] 0 0
Hradec Králové
Country [24] 0 0
Finland
State/province [24] 0 0
Helsinki
Country [25] 0 0
France
State/province [25] 0 0
Pessac
Country [26] 0 0
France
State/province [26] 0 0
Poitiers
Country [27] 0 0
Greece
State/province [27] 0 0
Athens
Country [28] 0 0
Greece
State/province [28] 0 0
Rio
Country [29] 0 0
Israel
State/province [29] 0 0
Jerusalem
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Madrid
Country [32] 0 0
Spain
State/province [32] 0 0
Salamanca
Country [33] 0 0
Spain
State/province [33] 0 0
Zaragoza
Country [34] 0 0
Turkey
State/province [34] 0 0
Ankara
Country [35] 0 0
Turkey
State/province [35] 0 0
Bornova
Country [36] 0 0
Turkey
State/province [36] 0 0
Istanbul
Country [37] 0 0
United Kingdom
State/province [37] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Cellectar Biosciences, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Part A of this study evaluates iopofosine I 131 (CLR 131) in patients with select B-cell
malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small
lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia
(WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma
(DLBCL), and central nervous system lymphoma (CNSL) who have been previously treated with
standard therapy for their underlying malignancy. Part B (CLOVER-WaM) is a pivotal efficacy
study evaluating IV administration of iopofosine I 131 in patients with WM that have received
at least two prior lines of therapy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02952508
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jarrod Longcor
Address 0 0
Cellectar Biosciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kate Oliver
Address 0 0
Country 0 0
Phone 0 0
608-327-8125
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02952508