Clinical Trials /

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

NCT04466475

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: RG1006317
  • SECONDARY ID: NCI-2019-06979
  • SECONDARY ID: RG1006317
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: R01CA205248
  • NCT ID: NCT04466475

Conditions

  • CD38 Positive
  • Plasma Cell Myeloma

Interventions

DrugSynonymsArms
Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10211At-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-B10Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)
MelphalanAlanine 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-19813Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (211At-OKT10-B10, melphalan, PBSC transplantation)ExperimentalPatients 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.
  • Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10
  • Melphalan

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:Up to 30 days post-transplant
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Achievement of response
Time Frame:Between days +80 to +90 post-transplant
Safety Issue:
Description: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.
Measure:Duration of response
Time Frame:From response (PR or better) to disease relapse or death, assessed up to 5 years
Safety Issue:
Description:Duration of response will be estimated using Kaplan-Meier methodology.
Measure:Overall survival
Time Frame:From transplantation to death, assessed up to 2 years post-transplant
Safety Issue:
Description:Kaplan-Meier methodology will be used to estimate the 2-year overall survival.
Measure:Progression-free survival
Time Frame:From transplantation to disease relapse or death, assessed up to 2 years post-transplant
Safety Issue:
Description:Kaplan-Meier methodology will be used to estimate the 2-year progression-free survival.
Measure:Rates of minimal residual disease (MRD)
Time Frame:At days 28, and +80 to +90 post-transplant
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

Last Updated

July 8, 2020