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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04466475
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Fred Hutchinson Cancer Research Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Damian J. Green
Principal Investigator Affiliation Fred Hutch/University of Washington Cancer Consortium
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherNIHNIH
Overall Status Not yet recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

CD38 Positive, Plasma Cell Myeloma
Additional Details

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.

Arms & Interventions

Arms

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

Given IV

Drug: - Melphalan

Given via infusion

Procedure: - Peripheral Blood Stem Cell Transplantation

Undergo PBSC transplantation

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Seattle, Washington

Status

Address

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

Site Contact

Damian J. Green

dgreen@fredhutch.org

206-667-5398