For Relapsed or Refractory Select B-Cell Malignancies

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Trial Summary

Official Title

An Open-Label, Multicenter, Phase 2 Study of CLR 131 in Patients With Relapsed or Refractory (R/R) Select B-Cell Malignancies

Status

Recruiting

Condition

Multiple Myeloma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma, Marginal Zone Lymphoma, Mantle-Cell Lymphoma, Diffuse Large B Cell Lymphoma

Actual Start Date

July 26, 2017

Estimated Primary Completion Date

December 2018

About the Trial

Study of CLR 131 in Relapsed or Refractory Select B-Cell Malignancies

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.

CLR 131 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 (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). Radio iodinated CLR1404 has been evaluated in over 60 xenografts and spontaneous (transgenic) tumor models. In all but two cases of hepatocellular carcinoma, CLR1404 demonstrated selective cancer cell uptake and retention. In various rodent tumor models, CLR 131 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, the radio sensitivity of these cancers, and initial preclinical and clinical experience with radio iodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 2 trial.

Detailed Info

Brief Summary

This study evaluates CLR 131 in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL) who have been previously treated with standard therapy for their underlying malignancy.

Study Phase

Phase 2

Estimated Enrollment

80

Estimated Primary Completion Date

December 2018

Study Type

Interventional

Interventions
  • Drug: CLR 131
Sponsor

Cellectar Biosciences, Inc.

Eligibility

Gender

Male & Female

18+

Age

18 years and older

Inclusion Criteria


All Patients

  • Histologically or cytologically confirmed MM; CLL/SLL, LPL, MZL; or MCL OR histologically proven, de novo, DLBCL
  • ECOG performance status of 0 to 2
  • 18 years of age or older
  • Life expectancy of at least 6 months
  • Platelets ≥ 100,000/µL (if full-dose anticoagulation therapy is used, platelets ≥ 150,000/µL are required)
  • WBC count ≥ 3000/µL
  • Absolute neutrophil count ≥ 1500/µL
  • Hemoglobin ≥ 9 g/dL (last transfusion, if any, must be at least one 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
  • Patient is judged by the Investigator to have the initiative and means to be compliant with the protocol and be within geographical proximity to make the required study visits
  • Patient or his or her legal representative has the ability to read, understand, and provide written informed consent for the initiation of any study-related procedures
  • Female patients of childbearing potential must have a negative pregnancy test within 24 hours of dosing
  • Women of childbearing potential and men who are able to father a child must agree to use an effective method of contraception (e.g. oral contraceptives, double-barrier methods such as a condom and a diaphragm, intrauterine device, Norplant, Depo-Provera) during the study and for 12 months following administration of the study drug

Patients with Multiple Myeloma

  • At least 2 prior regimens, which must include at least one approved proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) and at least one approved immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide), with or without maintenance therapy, unless patients are ineligible to receive such agents.
  • Bone marrow biopsy within 28 days of CLR 131 infusion demonstrating at least 5% plasma cell involvement
  • 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
  • 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.
    • Measurable plasmacytoma
  • 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, 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 one prior antibiotic regimen for H pylori
  • At least one measurable nodal lesion with longest diameter > 15 mm or one measurable extra nodal lesion (e.g. hepatic nodule) with longest diameter > 10 mm

Patients with Mantle Cell Lymphoma

  • Prior treatment with at least one prior regimen
  • At least one measurable nodal lesion with longest diameter > 15 mm or one measurable extra nodal lesion (e.g. hepatic nodule) with longest diameter > 10 mm

Patients with Diffuse Large B-Cell Lymphoma

  • Relapsed or refractory to combination chemotherapy for DLBCL that contains rituximab and an anthracycline. 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 one line of therapy or with PD ≤ 3 months of the most recent chemotherapy regimen.
  • At least one measurable nodal lesion with longest diameter > 15 mm or one measurable extra nodal lesion (e.g. hepatic nodule) with longest diameter > 10 mm

Exclusion Criteria

  • Ongoing Grade 2 or greater toxicities due to previous therapies. Stable, tolerable Grade 2 AEs (e.g. 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
  • 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 [e.g. 81 mg daily] for cardioprotection)
  • PTT > 1.3 √ó ULN
  • INR > 2.5
  • Radiation therapy, chemotherapy, immunotherapy, or investigational therapy within 2 weeks of eligibility-defining bone marrow biopsy.
  • History of hypersensitivity to iodine
  • Any other concomitant serious illness or organ system dysfunction that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug including, but not limited to, myelodysplastic syndromes; New York Heart Association class III-IV heart disease; unstable angina pectoris; serious cardiac arrhythmia requiring medication or a pacemaker/automatic implantable cardioverter defibrillator; myocardial infarction within the past 6 months; uncontrolled hypertension; severe peripheral vascular disease; ongoing hemodialysis or peritoneal dialysis; poorly controlled severe chronic obstructive pulmonary disease; ongoing/active infection requiring antibiotics; and uncontrolled hypothyroidism or hyperthyroidism
  • Major surgery within 6 weeks of enrollment
  • Known history of human immunodeficiency virus, hepatitis C, or hepatitis B infection
  • Pregnancy or breast-feeding

Enrollment

For more information on enrollment into the current CLR 131 trial, please contact us or visit clinicaltrials.gov for location information.

Contact Us Visit ClinicalTrials.gov

Frequently Asked Questions

Clinical trials are research studies that involve people. Through clinical trials, 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 trials 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 trials, 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 trials are an option to think about. Trials 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 trial has a person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the trial, called a protocol. The protocol explains what will be done during the trial. 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 trial
  • Who can join the trial (called “eligibility criteria”)
  • How many people are needed for the trial
  • 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 Trial 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 trials 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 trials 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 trials 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 trials are treated like guinea pigs

FACT: Clinical trial patients often report that they have been treated with the utmost care, compassion and respect during their clinical trial treatment(s). Also, clinical trials 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 trial will receive the best treatment available to treat their type and stage of cancer. Placebos are very rarely used in cancer clinical trials 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 trials are unaffordable and/or not covered by insurance

FACT: Volunteers for clinical trials rarely have to pay any costs related to participating in the trial. There are two types of costs associated with a clinical trial: research costs and patient care costs. Research costs are those associated with conducting the trial, 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 trial, such as the costs for routine care including doctor visits, hospital stays, clinical laboratory tests, x-rays and other clinical trial-related activities that would be done even if you were not in the trial. Many health insurance carriers will cover patient care costs, but you should ask the clinical trial research team which costs will be your responsibility and also check with your health insurance carrier about the coverage they provide for clinical trial participants before making the decision about participating in a clinical trial.6


Myth #4: Clinical trials 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 trials for other reasons. Cancer clinical trials are available for people at all stages of their disease.5


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

FACT: Clinical trials rely on voluntary participation. You are free to leave a clinical trial 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 trial 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 trial available that might help me, my doctor will definitely tell me about it.

FACT: Your doctor may not know about all available clinical trials that might benefit you. The National Institutes of Health has an online database that you, your family or doctor can search to find appropriate trials: www.clinicaltrials.gov. Alternatively, it’s often worth making contact with 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 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 trials are reviewed by the country's regulatory department. For example, in the US, clinical trials 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 trial must have the study reviewed and approved by an Institutional Review Board (IRB). The IRB reviews all aspects of a clinical trial to make sure that the rights, safety, and well-being of trial participants will be protected. The IRB must also review ongoing trials at least yearly and, based on those reviews, can decide whether the trial should continue as initially planned or if changes should be made to improve participant protection. An IRB can stop a clinical trial if the researchers are not following the protocol or if the trial 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 trial 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. Trials taking place at multiple locations can involve multiple IRBs.

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

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 trial. Similar to IRBs, DSMBs review the progress of a clinical trial and participant safety, but they also review data on the effectiveness of the trial interventions. DSMB members are experts in clinical research and clinical trials. They ensure that trial data are complete, and they can stop a trial early if safety concerns arise or if an answer to the main research question is obtained earlier than expected. Stopping a trial early because the main research question has been answered may make it possible for people who are not in the trial 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

References:

  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.