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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02952508
Ethics application status
Date submitted
28/10/2016
Date registered
2/11/2016
Date last updated
19/09/2024

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
Active, not 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
22/12/2026
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
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United States of America
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New Jersey
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United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
Country [17] 0 0
United States of America
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Washington
Country [18] 0 0
United States of America
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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
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Greece
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Rio
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Israel
State/province [29] 0 0
Jerusalem
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
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Spain
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Madrid
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Spain
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Salamanca
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Spain
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Zaragoza
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Turkey
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Ankara
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Turkey
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Bornova
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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
Trial website
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
clinical@cellectar.com
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02952508