Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma

NCT02278315 | Completed Phase 1 DMC

• 1 other identifier: DCL-14-002
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of the study is to determine the safety and tolerability of I-131-CLR1404 as a single or multiple dose, with and without concurrent weekly dexamethasone, in patients with relapsed or refractory multiple myeloma who have previously been treated with, or are intolerant of, an immunomodulator and a proteasome inhibitor.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Radiopharmaceutical; Therapy; Phase 1

Outcome Measures

Primary Outcomes (1)

• Number of participants with dose limiting toxicities (DLT)

  DLT will be assessed by physical examination, vital signs, ECG, and laboratory values

  up to 85 days

Secondary Outcomes (3)

• Identification of recommended phase 2 dose of I-131-CLR1404 with concurrent weekly dexamethasone

  until non-tolerated dose is defined; dose escalation descision made upon review of data from a complete cohort (85 days after all subjects in cohort have received infusion)

• Identification of recommended phase 2 dose of I-131-CLR1404 without dexamethasone

  until non-tolerated dose is defined; dose escalation descision made upon review of data from a complete cohort (85 days after all subjects in cohort have received infusion)

• Identify the recommended dosing schedule of I-131-CLR1404, in relapsed or refractory MM

  until non-tolerated dose is defined with both dosing regimens; dose escalation decision made upon review of data from a complete cohort (85 days after all subjects in cohort have received infusion)

Other Outcomes (1)

• Determination of therapeutic activity of I-131-CLR1404 in relapsed or refractory multiple myeloma

  through Day 85

Study Arms (1)

Single

EXPERIMENTAL

I-131-CLR1404 with or without concurrent dexamethasone

Drug: I-131-CLR1404; Drug: dexamethasone

Interventions

I-131-CLR1404 DRUG

Single IV dose of I-131-CLR1404, increased/decreased by cohort

Also known as: 131I-CLR1404, 18-(p-[I-131]-iodophenyl)octadecyl phosphocholine, CLR 131

Single

dexamethasone DRUG

40 mg dexamethasone orally once weekly for up to 12 weeks

Also known as: Decadron

Single

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed multiple myeloma
• Prior treatment with or intolerance to proteasome inhibitor and immunomodulator
• Bone marrow biopsy within 28 days of study drug infusion demonstrating at least 5% plasma cell involvement
• Progressive disease defined by any of following:
• % increase in serum M-protein from lowest response value during (or after) last therapy and/or absolute increase in serum M-protein of \> or equal to 0.5 g/dL; 25% increase in urine M-protein from lowest response value during (or after) last therapy and/or absolute increase in urine M-protein of \> or equal to 200 mg/24h; 25% increase in bone marrow plasma cell percentage from lowest response value during (or after) last therapy - absolute bone marrow plasma cell percentage must be \> or equal to 10% unless prior complete response when absolute bone marrow plasma cell percentage must be \> or equal to 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 following: Serum M-protein \> 1 g/dL; Urine M-protein \> 200 mg/24h; Serum free light chain (FLC) assay: involved FLC level \> or equal to 10 mg/dL provided serum FLC ratio is abnormal; subjects who are non-secretors will be considered on a case-by-case basis
• Eastern Cooperative Oncology Group performance status of 0 to 2
• Life expectancy of at least 6 months
• Have initiative and means to be compliant with protocol and within geographical proximity to make required study visits as judged by Investigator
• Subject or legal representative has ability to read, understand and provide written informed consent for study related procedures
• Women of childbearing potential must have negative pregnancy test within 24 hours of enrollment
• Women of childbearing potential and men who are able to father a child, must agree to use an effective contraception method during study and for 12 months following study drug administration

You may not qualify if:

• Grade 2 or greater toxicities due to previous therapies, subject to laboratory abnormalities listed below. Stable, tolerable Grade 2 adverse events may be allowed at discretion of Investigator
• Prior external beam radiation therapy resulting in greater than 20% total bone marrow receiving greater than 20 Gy
• Prior radioisotope therapy
• 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 spinal cord
• Subject has any of following laboratory abnormalities: WBC \< 3000/uL; ANC \< 1500/uL; Hemoglobin \< 8 g/dL; Estimated glomerular filtration rate \< 30 mL/min/1.73 m2; ALT \> 3 x ULN ; Bilirubin \> 1.5 x ULN
• Platelet count \< 100,000/uL without full-dose anticogulation therapy
• Platelet count \< 150,000/uL with ongoing full-dose anticoagulation therapy
• Clinically significant bleeding event, as judged by investigator, within prior 6 months
• Chronic immunosuppressive therapy
• Anti-platelet therapy, except low-dose aspirin for cardioprotection
• PTT \> 1.3 x ULN
• INR \> 1.3
• Radiation therapy, chemotherapy, immunotherapy, investigational therapy or corticosteroid use within 2 weeks of or after eligibility-defining bone marrow biopsy. Bisphosphonates and denosumab are permitted if subject has been receiving for at least 90 days
• History of hypersensitivity to iodine

Sponsors & Collaborators

• Cellectar Biosciences, Inc.: lead

Study Sites (4)

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Weichert JP, Clark PA, Kandela IK, Vaccaro AM, Clarke W, Longino MA, Pinchuk AN, Farhoud M, Swanson KI, Floberg JM, Grudzinski J, Titz B, Traynor AM, Chen HE, Hall LT, Pazoles CJ, Pickhardt PJ, Kuo JS. Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy. Sci Transl Med. 2014 Jun 11;6(240):240ra75. doi: 10.1126/scitranslmed.3007646.

  PMID: 24920661 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

CLR1404; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Natalie S Callander, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: October 30, 2014
• Study Start: February 1, 2015
• Primary Completion: December 9, 2020
• Study Completion: August 10, 2022
• Last Updated: February 22, 2023

Record last verified: 2023-02

Locations

US (4)