Radioimmunotherapy (211At-OKT10-B10) and Chemotherapy (Melphalan) Before Stem Cell Transplantation for the Treatment of Multiple Myeloma

NCT04466475 | Withdrawn Phase 1 DMC FDA Drug

• 4 other identifiers: RG1006317NCI-2019-0697910306R01CA205248
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of 211At-OKT10-B10 when given together with melphalan before a stem cell transplantation in treating patients with multiple myeloma. The radioimmunotherapy drug 211At-OKT10-B10 is a monoclonal antibody, called OKT10-B10, linked to a radioactive substance called 211At. OKT10-B10 attaches to CD38 positive cancer cells in a targeted way and delivers 211At to kill them. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving 211At-OKT10-B10 with melphalan before a stem cell transplant may kill more cancer cells.

Conditions

Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  Defined a true dose limiting toxicity (DLT) probability of 25% of subjects, where a DLT is defined as any grade 3-5 nonhematologic regimen-related toxicity within the first 30 days following autologous hematopoietic cell transplantation.

  Up to 30 days post-transplant

Secondary Outcomes (5)

• Achievement of response

  Between days +80 to +90 post-transplant

• Duration of response

  From response (PR or better) to disease relapse or death, assessed up to 5 years

• Overall survival

  From transplantation to death, assessed up to 2 years post-transplant

• Progression-free survival

  From transplantation to disease relapse or death, assessed up to 2 years post-transplant

• Rates of minimal residual disease (MRD)

  At days 28, and +80 to +90 post-transplant

Study Arms (1)

Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)

EXPERIMENTAL

Patients receive 211At-OKT10-B10 IV continuously on day -10 to day - 4 (approximately day -7) and melphalan via infusion on day -2. Patients then undergo HCT on day 0.

Biological: Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10; Drug: Melphalan; Procedure: Peripheral Blood Stem Cell Transplantation

Interventions

Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10 BIOLOGICAL

Given IV

Also known as: 211At-OKT10-B10, [211At]OKT10-B10, Astatine 211-labeled Anti-CD38 Monoclonal Antibody OKT10-B10, Astatine At 211 Anti-CD38 MoAb OKT10-B10, Astatine-211-OKT10-B10, At211-OKT10-B10

Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)

Melphalan DRUG

Given via infusion

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo PBSC transplantation

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)

Eligibility Criteria

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

You may qualify if:

• Patients with a diagnosis of multiple myeloma
• Patients must have autologous hematopoietic stem cells collected with a minimum CD34+ stem cell yield of \>= 4 x 10\^6 CD34+ cells/kg of body weight
• Subjects must have disease meeting criteria for clinical relapse or progressive disease (International Myeloma Working Group \[IMWG\] consensus criteria) and a history of \>= 1 prior autologous stem cell transplant(s)
• Subjects must have received at least 3 prior lines of therapy: an immunomodulatory drug, a proteasome inhibitor, and a CD38-targeting antibody
• \* Aline of therapy is defined as one or more cycles of a planned treatment program. This may consist of one or more planned cycles of a single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation, followed by maintenance is considered one line of therapy. A new line of therapy starts when a planned course of therapy is modified to include other treatment agents (alone or in combination) as a results of disease progression, relapse, or toxicity. A new line of therapy also starts when a planned period of observation off therapy is interrupted by a need for additional treatment for the disease
• Subjects must have an estimated creatinine clearance greater than 60 ml per minute by the following formula (Cockcroft-Gault). Serum creatinine value must be within 28 +/- days prior to registration
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) score =\< 2 or Karnofsky score \>= 70%
• Ability to provide informed consent
• Subjects 18 years of age

You may not qualify if:

• Subjects with a history of plasma cell leukemia
• History of central nervous system involvement by multiple myeloma
• Prior radioimmunotherapy or radiation of \> 20 Gy to pelvis or at maximally tolerated levels to any critical normal organ
• Prior allogeneic hematopoietic cell transplant
• More than 2 prior autologous hematopoietic cell transplants
• Subjects with medullary or extramedullary plasmacytoma/s measuring \> 3 cm by magnetic resonance imaging (MRI) or positron emission tomography (PET)-computed tomography (CT) (radiated lesions are exempt from this criterion)
• Subjects with a history of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease as determined by the principal investigator (PI) or designee
• Subjects with corrected QT (QTc) prolongation at baseline
• Subjects with a history of cardiac arrhythmia and a heart rate \> 100 beats per minute (BPM) (oral beta-blocker \[excluding sotalol\] and/or calcium channel blocker therapy are acceptable to achieve rate control)
• History of reactive airway disease and clinically significant asthma requiring any form of medical treatment in the prior three months
• Left ventricular ejection fraction \< 40%
• Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) \< 50% or receiving supplemental continuous oxygen
• Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease.
• Bilirubin \> 2 times the upper limit of normal
• Aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\] \> 2 times the upper limit of normal

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Peripheral Blood Stem Cell Transplantation

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)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Damian J. Green

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 8, 2020
• First Posted: July 10, 2020
• Study Start: January 27, 2024
• Primary Completion: October 1, 2025
• Study Completion (Estimated): September 30, 2027
• Last Updated: January 31, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)