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

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ClinicalTrials.gov Identifier: NCT04466475
Recruitment Status : Not yet recruiting
First Posted : July 10, 2020
Last Update Posted : September 2, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE July 8, 2020
First Posted Date  ICMJE July 10, 2020
Last Update Posted Date September 2, 2020
Estimated Study Start Date  ICMJE October 1, 2020
Estimated Primary Completion Date March 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2020)
Maximum tolerated dose [ Time Frame: Up to 30 days post-transplant ]
Defined as the occurrence of dose limiting toxicities (DLTs) in 25% of patients, where a DLT is defined as the occurrence of grade III/IV regimen-related toxicity as defined by the Bearman Scale.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2020)
  • Achievement of response [ Time Frame: Between days +80 to +90 post-transplant ]
    Measured per the International Myeloma Working Group criteria. The response rates (partial response [PR] or better) will be estimated along with the exact 95% confidence interval.
  • Duration of response [ Time Frame: From response (PR or better) to disease relapse or death, assessed up to 5 years ]
    Duration of response will be estimated using Kaplan-Meier methodology.
  • Overall survival [ Time Frame: From transplantation to death, assessed up to 2 years post-transplant ]
    Kaplan-Meier methodology will be used to estimate the 2-year overall survival.
  • Progression-free survival [ Time Frame: From transplantation to disease relapse or death, assessed up to 2 years post-transplant ]
    Kaplan-Meier methodology will be used to estimate the 2-year progression-free survival.
  • Rates of minimal residual disease (MRD) [ Time Frame: At days 28, and +80 to +90 post-transplant ]
    MRD will be assessed using multi-color flow cytometry and next generation sequencing in conjunction with functional imaging (i.e., positron emission tomography-computed tomography). The proportion who achieve MRD will be estimated along with an exact 95% confidence interval.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radioimmunotherapy (211At-OKT10-B10) and Chemotherapy (Melphalan) Before Stem Cell Transplantation for the Treatment of Multiple Myeloma
Official Title  ICMJE A Phase I Trial Evaluating Escalating Doses of 211At-Labeled Anti-CD38 Monoclonal Antibody (211At-OKT10-B10) Combined With Melphalan as Conditioning Prior to Autologous Hematopoietic Cell Transplantation for Patients With Multiple Myeloma
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.
Detailed Description

OUTLINE: This is a dose-escalation study of 211At-OKT10-B10.

Patients receive 211At-OKT10-B10 intravenously (IV) continuously on days -7 to -4 and melphalan via infusion on day -2. Patients then undergo peripheral blood stem cell (PBSC) transplantation on day 0.

After completion of study treatment, patients are followed for 30 days, between 80 and 90 days, at 6, 9, 12, 18, and 24 months, and then annually thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • CD38 Positive
  • Plasma Cell Myeloma
Intervention  ICMJE
  • Biological: Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10
    Given IV
    Other Names:
    • 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
  • Drug: Melphalan
    Given via infusion
    Other Names:
    • 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
  • Procedure: Peripheral Blood Stem Cell Transplantation
    Undergo PBSC transplantation
    Other Names:
    • PBPC transplantation
    • PBSCT
    • Peripheral Blood Progenitor Cell Transplantation
    • Peripheral Stem Cell Support
    • Peripheral Stem Cell Transplant
    • Peripheral Stem Cell Transplantation
Study Arms  ICMJE Experimental: Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)
Patients receive 211At-OKT10-B10 IV continuously on days -7 to -4 and melphalan via infusion on day -2. Patients then undergo PBSC transplantation on day 0.
Interventions:
  • Biological: Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10
  • Drug: Melphalan
  • Procedure: Peripheral Blood Stem Cell Transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 8, 2020)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2026
Estimated Primary Completion Date March 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with a diagnosis of multiple myeloma
  • Patients must have demonstrated at least a partial response (PR) according to the International Myeloma Working Group (IMWG) criteria to at least one induction regimen
  • Patients must have autologous hematopoietic stem cells collected with a minimum CD34+ stem cell yield of 8 x 10^6 CD34+ cells/kg of body weight (sufficient for two autologous hematopoietic cell transplantations [HCTs])
  • Patients must have an estimated creatinine clearance greater than 60 ml per minute by Cockcroft-Gault formula. Serum creatinine value must be within 28 +/- 2 days prior to registration
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) score =< 2 or Karnofsky score >= 70%
  • Patients must have history of CD38+ myeloma cells as demonstrated by either flow cytometry or immunohistochemistry
  • For patients of childbearing potential, must have a negative urinary pregnancy test on the day of infusion of 211At-OKT10-B10
  • Ability to provide informed consent

Exclusion Criteria:

  • Patients 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
  • Patients 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)
  • Patients with symptomatic coronary artery disease or uncontrolled arrhythmia
  • 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
  • Patients who are known to be seropositive for human immunodeficiency virus (HIV)
  • Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin [HCG]+) or breast feeding
  • Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant
  • Patients with untreated and uncontrolled infection at time of enrollment
  • Patients with known amyloid light-chain (AL) subtype amyloidosis
  • Known allergy to murine-based monoclonal antibodies
  • Known contraindications to radiotherapy
  • History of another primary malignancy that has not been in remission for at least 2 years (the following are exempt from the 2-year limit: non-melanoma skin cancer, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou [PAP] smear)
  • Any anti-CD38 monoclonal antibody within 3 months of anticipated date of infusion of 211At-OKT10-B10
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Damian J. Green 206-667-5398 dgreen@fredhutch.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04466475
Other Study ID Numbers  ICMJE RG1006317
NCI-2019-06979 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RG1006317 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
R01CA205248 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Damian J. Green Fred Hutch/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP