Cellectar Biosciences, Inc.

Waldenstrom’s Macroglobulinemia Pivotal Study

Study Summary

Official 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)

Status

Active, not recruiting

Condition

Waldenstrom Macroglobulinemia, Multiple Myeloma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Diffuse Large B Cell Lymphoma, Central Nervous System Lymphoma

Actual Start Date

July 26, 2017

Estimated Primary Completion Date

December 22, 2024

About the Study

Study of iopofosine in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia

B-cell malignancies represent a diverse collection of diseases and taken together, make up the majority of hematologic malignancies. B-cell lymphomas represent the largest percentage of these neoplasms, and the relapsed and/or refractory B-cell lymphomas have proven very difficult to treat. Success rate, defined as complete or partial response, is as low as 2% to 4% in many of these diseases, and they remain an area of a significant unmet medical need. Patients that have failed BTKi, including WM patients, represent a very challenging patient population with significantly reduced life-expectancy.

Iopofosine is a radio iodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR 1404) is radiolabeled with the isotope iodine-131 (I-131). Radio iodinated CLR 1404 has been evaluated in over 60 xenografts and spontaneous (transgenic) tumor models. In all but two cases of hepatocellular carcinoma, CLR 1404 demonstrated selective cancer cell uptake and retention. In various rodent tumor models, iopofosine has also demonstrated tumor growth delay and prolongation of survival.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in B-cell malignancies, Cellectar Biosciences has chosen to assess iopofosine in a pivotal expansion cohort in heavily pretreated Waldenstrom’s macroglobulinemia patients.

Detailed Info

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.

Study Phase

Phase 2

Estimated Enrollment

120

Estimated Primary Completion Date

December 22, 2024

Study Type

Interventional

Interventions
  • Drug: Iopofosine I 131 single dose
  • Drug: Iopofosine I 131 multiple dose
  • Drug: Iopofosine I 131 fractionated dose
Sponsor

Cellectar Biosciences, Inc.

Eligibility

Gender

Male & Female

18+

Age

18 years and older

View Inclusion Criteria

Inclusion Criteria

[CLOVER-1] Inclusion Criteria: All Patients

  • Histologically or cytologically confirmed MM; CLL/SLL, LPL/WM, MZL; or MCL OR histologically proven, DLBCL. Patients with transformed DLBCL are allowed.
  • 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
  • Alanine aminotransferase <3 × 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 2 prior regimens, which must include at least 1 approved proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) and at least 1 approved immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide), with or without maintenance therapy, unless patients are intolerable to such agents or ineligible to receive such agents.

  • 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.
  • Patients who are non-secretors will be considered for accrual on a case-by-case basis by the Sponsor and will require an Investigator plan to define PD prior to enrollment and to assess clinical benefit after treatment.

Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma/Waldenstrom’s 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.

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.

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.

[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 first line standard of care
  • Failed treatment with a BTK inhibitor or had a sub-optimal response to it.

Exclusion Criteria

[CLOVER-1] 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
  • Central nervous system involvement unless previously treated with surgery or radiotherapy with the patient neurologically stable and off corticosteroids
  • 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 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.

[CLOVER-WaM] Exclusion Criteria

  • 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.
  • 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 infusion.
  • Radiation therapy, chemotherapy, immunotherapy within 2 weeks, and investigational therapy within 5 half-lives of eligibility-defining bone marrow biopsy.

Enrollment

For more information on enrollment into the current iopofosine study, please contact us or visit clinicaltrials.gov for location information.

Contact Us Visit ClinicalTrials.gov

Frequently Asked Questions

Clinical trials (or clinical studies) are research studies that involve people. Through clinical studies, doctors find new ways to improve treatments and the quality of life for people with disease.

Researchers design cancer clinical trials to test new ways to:

  • Treat cancer
  • Find and diagnose cancer
  • Prevent cancer
  • Manage symptoms of cancer and side effects from its treatment

Clinical studies are the final step in a long process that begins with research in a lab. Before any new treatment is used with people in clinical studies, researchers work for many years to understand its effects on cancer cells in the lab and in animals. They also try to figure out the side effects it may cause.

Any time you or a loved one needs treatment for cancer, clinical studies are an option to think about. Studies are available for all stages of cancer. It is a myth that they are only for people who have advanced cancer that is not responding to treatment.

Every study has a person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol. The protocol explains what will be done during the study. It also contains information that helps the doctor decide if this treatment is right for you. The protocol includes information about:

  • The reason for doing the study
  • Who can join the study (called “eligibility criteria”)
  • How many people are needed for the study
  • Any drugs or other treatments that will be given, how they will be given, the dose, and how often
  • What medical tests will be done and how often
  • What types of information will be collected about the people taking part3

Clinical Study Phases and Their Purpose(s)

Phase 1

  • Find a safe dose
  • Decide how the treatment/medicine should be administered
  • Determine how the new treatment may impact the people who take it

Phase 2

  • Determine if the treatment has an effect on certain cancers or cancer types
  • Determine how the new treatment may impact the people who take it

Phase 3

  • Compare and contrast the treatment with the current standard treatment

Phase 4

  • Monitor and further asses the long-term safety and efficacy of the treatment
  • According to the National Cancer Institute, clinical studies are finding and creating new ways of treating, diagnosing and even preventing cancer so that ultimately, care and quality of life for people with cancer can improve.1
  • In addition to testing new ways of treating and diagnosing cancer, clinical studies are also used to determine the best uses and combinations of existing therapies to combat cancer and to improve patient care and quality of life for cancer patients both during and after their treatments.1
  • Ultimately, thousands of people have volunteered over the years for clinical studies, and it is because of those patients, and dedicated medical and research personnel that we now have so many breakthroughs in disease and cancer prevention within the last 50 years.2

Myth #1: Patients who are involved in clinical studies are treated like guinea pigs

FACT: Clinical study patients often report that they have been treated with the utmost care, compassion and respect during their clinical study treatment(s). Also, clinical studies are highly regulated, and many safeguards have been put into place to protect patients and their best interest.6

Myth #2: Some patients receive placebos, and some receive the real treatments

FACT: All patients who enroll in a clinical study will receive the best treatment available for their type and stage of cancer. Placebos are very rarely used in cancer clinical studies and if they are, they are given in addition to the current standard of care and the patient is told that it is happening.4

Myth #3: Clinical studies are unaffordable and/or not covered by insurance

FACT: Volunteers for clinical studies rarely must pay any costs related to participating in the study. There are two types of costs associated with a clinical study: research costs and patient care costs. Research costs are those associated with conducting the study, such as data collection and management, research physician and nurse time, analysis of results, and tests performed purely for research purposes. These costs are usually covered by the sponsoring organization, such as the biopharmaceutical company, and are not the patient's responsibility. Patient care costs are costs that are not covered by the research sponsors doing the clinical study, such as the costs for routine care including doctor visits, hospital stays, clinical laboratory tests, x-rays and other clinical study-related activities that would be done even if you were not in the study. Many health insurance carriers will cover patient care costs, but you should ask the clinical study research team which costs will be your responsibility and check with your health insurance carrier about the coverage they provide for clinical study participants before making the decision about participating in a clinical study.6

Myth #4: Clinical studies are only for people who have tried all other treatments and have run out of options.

FACT: Understanding the phases described above can help to answer this question. In some cases, the answer may be yes – if nothing else is working a Phase 1 trial may help you further research for others with your disease (and has a small chance of making a difference for you as well.) But usually, people participate in clinical studies for other reasons. Cancer clinical studies are available for people at all stages of their disease.5

Myth #5: Once a patient agrees to be involved in a clinical study, they are required to follow through to the end

FACT: Clinical studies rely on voluntary participation. You are free to leave a clinical study at any time, even after you have signed an informed consent and received the investigational drug or placebo. However, you should always let the clinical study team know before you decide to leave the trial because some medicines cannot be stopped safely without a doctor’s help.6

Myth #6: If there is a clinical study available that might help me, my doctor will tell me about it.

FACT: Your doctor may not know about all available clinical studies that might benefit you. The National Institutes of Health has an online database that you, your family or doctor can search to find appropriate studies: www.clinicaltrials.gov. Alternatively, it’s often worth contacting a patient advocacy organization to help you navigate the process. Many of them have tailored services that can help you with your search and help you understand the options.
If you are thinking about participating in a clinical study and have additional questions, you should talk to your doctor or a patient advocacy organization for your disease or condition.

 If you are thinking about participating in a clinical trial and have additional questions, you should talk to your doctor or a patient advocacy organization for your disease or condition.6

National and international regulations and policies have been developed to help ensure that research involving people is conducted according to strict scientific and ethical principles. In these regulations and policies, people who participate in research are usually referred to as "human subjects."

Clinical studies are reviewed by the country's regulatory department. For example, in the U.S, clinical studies are reviewed by the U.S. Food and Drug Administration (FDA) and in Canada that review is done by Health Canada.

In addition, each hospital that conducts a clinical study must have the study reviewed and approved by an Institutional Review Board (IRB). The IRB reviews all aspects of a clinical study to make sure that the rights, safety, and well-being of study participants will be protected. The IRB must also review ongoing studies at least yearly and, based on those reviews, can decide whether the study should continue as initially planned or if changes should be made to improve participant protection. An IRB can stop a clinical study if the researchers are not following the protocol or if the study appears to be causing unexpected harm to the study participants.

An IRB must have at least five members, including one scientist, one person who is not a scientist, and one person who is not affiliated with the institution where the study is taking place and who is not an immediate family member of someone who is affiliated with that institution. The nonscientist and the nonaffiliated member can be the same person. IRBs can also include doctors, nurses, social workers, chaplains, patient advocates, and other health care or community professionals. All members of an IRB are required to be educated about the IRB's purpose, functions, and responsibilities, as outlined in federal regulations. Studies taking place at multiple locations can involve multiple IRBs.

Clinical studies also may use a Data and Safety Monitoring Board (DSMB) or a safety monitoring committee to monitor the safety and progress of the studies.

A DSMB is a committee of doctors, statisticians, and others who are independent of the people, organizations, and institutions that are sponsoring, organizing, and conducting the clinical studies. Similar to IRBs, DSMBs review the progress of a clinical study and participant safety, but they also review data on the effectiveness of the study interventions. DSMB members are experts in clinical research and clinical studies. They ensure that study data are complete, and they can stop a study early if safety concerns arise or if an answer to the main research question is obtained earlier than expected. Stopping a study early because the main research question has been answered may make it possible for people who are not in the study to get access to an effective intervention sooner. DSMBs have scheduled meetings to review clinical data, and their meeting minutes or recommendations are forwarded to the IRBs.7

  1. "Clinical Trials." National Cancer Institute. National Institutes of Health. http://www.cancer.gov/research/areas/clinical-trials
  2. "The Importance of Clinical Trials - Policy and Medicine." Policy and Medicine. Policy and Medicine Online. http://www.policymed.com/2010/05/the-importance-of-clinical-trials.html
  3. "What Are Clinical Trials?" National Cancer Institute. National Institutes of Health. http://www.cancer.gov/about-cancer/treatment/clinical-trials/what-are-trials
  4. "Placebo." National Cancer Institute. National Institutes of Health. http://www.cancer.gov/about-cancer/treatment/clinical-trials/what-are-trials/placebo
  5. "Top 10 Myths About Clinical Trials for Cancer." https://www.verywell.com/myths-about-clinical-trials-for-cancer-2249004
  6. "Debunking Common Myths About Clinical Trials." Debunking Common Myths About Clinical Trials. Catalyst Pharma. http://catalyst.phrma.org/debunking-common-myths-about-clinical-trials
  7. "Cancer Clinical Trials."National Cancer Institute, National Institutes of Health. http://www.cancer.gov/research/areas/clinical-trials

The safety and efficacy of the investigational use of this product has not been determined. There is no guarantee that the investigational use listed will be filed with and/or approved for marketing by a regulatory agency.