Overview

²¹¹At-OKT10-B10 and Fludarabine Alone or in Combination With Cyclophosphamide and Low-Dose TBI Before Donor Stem Cell Transplant for the Treatment of Newly Diagnosed, Recurrent, or Refractory High-Risk Multiple Myeloma

Status:
Not yet recruiting
Trial end date:
2028-12-31
Target enrollment:
0
Participant gender:
All
Summary
This phase I trial investigates the side effects and best dose of ²¹¹At-OKT10-B10 when given together with fludarabine, alone or in combination with cyclophosphamide and low-dose total-body irradiation (TBI) before donor stem cell transplant in treating patients with high-risk multiple myeloma that is newly diagnosed, has come back (recurrent), or does not respond to treatment (refractory). ²¹¹At-OKT10-B10 is a monoclonal antibody, called OKT10-B10, linked to a radioactive agent called ²¹¹At. OKT10-B10 attaches to CD38 positive cancer cells in a targeted way and delivers ²¹¹At to kill them. Chemotherapy drugs, such as fludarabine and cyclophosphamide, 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. Radiation therapy such as TBI uses high energy x-rays to kill cancer cells and shrink tumors. Giving ²¹¹At-OKT10-B10 together with chemotherapy and TBI before a donor stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells stem cells to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Fred Hutchinson Cancer Research Center
Collaborator:
National Cancer Institute (NCI)
Treatments:
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Cyclophosphamide
Daratumumab
Fludarabine
Fludarabine phosphate
Immunoglobulins
Criteria
Inclusion Criteria:

- Patients with newly diagnosed or relapsed/refractory multiple myeloma

- Patients with multiple myeloma must have at least one of the following high-risk
features:

- t(4;14), t(14;16), t(14;20) or deletion 17p, gain in chromosome 1q (> 3 copies of
CKS1b) by fluorescence in situ hybridization (FISH); hypodiploidy; complex
karyotype

- Revised International Staging System III

- Plasmablastic morphology

- History of primary or secondary plasma cell leukemia

- Patients must start ²¹¹At-OKT10-B10 within 40-180 days of autologous stem cell
transplant (either as part of their induction, or as salvage)

- Patients must have an estimated creatinine clearance greater than 50/ml per minute
measured by 24-hour urine collection

- Total bilirubin < 2 times the upper limit of normal

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times the
upper limit of normal)

- Patients must have an Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky >=
70

- Patients must have CD38+ myeloma cells as demonstrated by either flow cytometry or
immunohistochemistry in most recent bone marrow that had evidence of clonal plasma
cells

- For patients of childbearing potential, must have a negative urinary pregnancy test on
the day of and prior to infusion of ²¹¹At-OKT10-B10

- Ability to provide informed consent

- Patients must have an HLA-matched related donor or an HLA-matched unrelated donor who
meets standard Seattle Cancer Care Alliance (SCCA) and/or National Marrow Donor
Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) or
bone marrow donation, as follows:

- Related donor: related to the patient and genotypically or phenotypically
identical for HLA-A, B, C, DRB1 and DQB1. Phenotypic identity must be confirmed
by high-resolution typing

- Unrelated donor:

- Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR

- Mismatched for a single allele without antigen mismatching at HLA-A, B, or C
as defined by high resolution typing but otherwise matched for HLA-A, B, C,
DRB1 and DQB1 by high resolution typing

- Donors are excluded when preexisting immunoreactivity is identified that
would jeopardize donor hematopoietic cell engraftment. The recommended
procedure for patients with 10 of 10 HLA allele level (phenotypic) match is
to obtain panel reactive antibody (PRA) screens to class I and class II
antigens for all patients before HCT. If the PRA shows > 10% activity, then
flow cytometric or B and T cell cytotoxic cross matches should be obtained.
The donor should be excluded if any of the cytotoxic cross match assays are
positive. For those patients with an HLA class I allele mismatch, flow
cytometric or B and T cell cytotoxic cross matches should be obtained
regardless of the PRA results. A positive anti-donor cytotoxic crossmatch is
an absolute donor exclusion

- Patient and donor pairs homozygous at a mismatched allele in the graft
rejection vector are considered a two-allele mismatch, i.e., the patient is
A*0101 and the donor is A*0102, and this type of mismatch is not allowed

- Patients without an HLA-matched related or unrelated donor available must have a
related donor who is identical for one HLA haplotype and mismatched at the HLA-A, -B
or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or DRB1
mismatches

Exclusion Criteria:

- History of central nervous system involvement by multiple myeloma

- Presence of circulating plasma cells in the peripheral blood of 5% or more by flow
cytometry or morphology

- Prior radioimmunotherapy or radiation of > 20 Gy to pelvis or at maximally tolerated
levels to any critical normal organ

- Prior allogeneic HCT

- More than two prior autologous HCTs

- Patients with plasmacytomas > 1 cm in bone marrow or any extramedullary plasmacytoma.
Previously fludeoxyglucose F-18 (FDG) avid mass lesions by positron emission
tomography (PET) that are no longer hypermetabolic following the most recent cycle of
therapy are exempt, as are plasmacytomas irradiated with curative intent (>= 35 Gy)

- Patients with symptomatic coronary artery disease defined as having angina or anginal
equivalent, and/or arrhythmias requiring anti-arrhythmics for rhythm control

- History of reactive airway disease and clinically significant asthma requiring ongoing
treatment

- Patients with the following organ dysfunction:

- Left ventricular ejection fraction < 40% in patients with HLA-matched or
unrelated donor or < 45% in patients with an HLA-haploidentical donor

- New York Heart Association (NYHA) class > 1 heart failure

- Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) < 50% or
receiving supplemental continuous oxygen. When pulmonary function tests cannot be
obtained, the 6-minute walk test (6MWT, also known as exercise oximetry) will be
used: Any patient with oxygen saturation on room air of < 90% during a 6MWT will
be excluded

- 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

- Patients who are known to be seropositive for human immunodeficiency virus (HIV)

- Perceived inability to tolerate diagnostic or therapeutic procedures

- 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

- Uncontrolled or untreated active infection

- Patients with known AL subtype amyloidosis

- Inability to understand or give an informed consent

- 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: nonmelanoma skin cancer,
curatively treated localized prostate cancer, or cervical carcinoma in situ or
squamous intraepithelial lesion on papanicolaou (PAP) smear

- Therapy with anti-CD38 monoclonal antibody within 3 months of ²¹¹At-OKT10-B10 infusion

- Prior therapy with radiolabeled monoclonal antibodies

- Any history of treatment with checkpoint inhibitor/s