Hairy cell leukemia (HCL) is a rare, slow-growing blood cancer in which the bone marrow makes
too many of certain white blood cells. The antibody Rituximab/Ruxience binds to a protein in
cancerous white blood cells and is often used to treat HCL. Researchers want to see if
combining it with the drug Moxetumomab pasudotox-tdfk (also called Lumoxiti) can fight HCL
To test the safety of Moxetumomab pasudotox taken with Rituximab/Ruxience for people with HCL
or HCL variant.
People age 18 years and older with HCL or HCL variant that has not responded to standard
Participants will be screened with:
Blood, heart, and urine tests
Test of blood oxygen levels
Review of bone marrow. This can be from previous test results or a new sample.
Participants will get the study drugs in up to 8 cycles. A cycle will last about 28 days.
The study drugs will be given through a plastic tube in a vein.
In the first week of cycle 1, participants will have:
1 visit to get Rituximab or Ruxience for 7.5 hours
3 visits to get Lumoxiti for 30 minutes per infusion
In the first week of cycles 2-8, participants will have:
visit to get Rituximab/Ruxience for 2-4 hours and Lumoxiti for 30 minutes
visits to get Lumoxiti for 30 minutes per infusion
Participants will be asked to drink lots of water and take aspirin during the cycles. They
will get drugs to minimize allergic reactions.
Participants will repeat screening tests at visits throughout the cycles and 1 follow-up
visit. They may have an eye exam.
Hairy cell leukemia (HCL) is an indolent CD22+ B-cell leukemia comprising 2% of all
leukemias, or approximately 1200 of the 62,130 new cases of leukemia/year in the US. HCL
variant (HCLv), also CD22+, is 10-20% as common as HCL, but more common in the
relapsed/refractory population due to its poor prognosis and response to standard purine
analog chemotherapy. HCLv cells are CD25-negative and wild type for BRAF, so HCLv
patients are not candidates for BRAF inhibitors. CD25+ classic-appearing HCL-cells that
express unmutated IGHV4-34 are wild-type for BRAF, remain brightly CD22 positive, and
confer a poor prognosis when treated with chemotherapy.
Moxetumomab pasudotox-tdfk is a recombinant immunotoxin containing a variable domain
(Fv) fragment of an anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin,
which kills CD22+ cells by binding to CD22 via the Fv fragment, and induction of
apoptotic cell death catalytic inhibition of protein synthesis in the cytosol.
Moxetumomab pasudotox-tdfk in phase 1 testing demonstrated a high complete response (CR)
rate in patients with chemoresistant HCL, without dose-limiting toxicity (DLT), but with
reversible grade 2 hemolytic uremic syndrome (HUS) not requiring plasmapheresis.
Moxetumomab pasudotox-tdfk completed multicenter phase 3 testing in 80 patients, meeting
its CR endpoint, with 8.8% incidence each of capillary leak syndrome (CLS, grade 3-4
2.5%), and HUS (grade 3-4 6.3%), both reversible.
Moxetumomab pasudotox-tdfk is the only known non-chemotherapy-containing regimen for HCL
which can consistently eradicate minimal residual disease (MRD), and this is associated
with prolonged CR durations. Recently, US Food and Drug Administration (FDA) has
accepted the Biologics License Application (BLA) for moxetumomab pasudotox-tdfk as the
treatment of adult patients with HCL.
Patients who did not achieve CR, or CR with MRD, often made neutralizing antibodies to
the bacterial-based toxin, and/or had collections of HCL cells not completely eradicated
by Moxetumomab pasudotox-tdfk. Both issues may be addressed by the addition of anti-CD20
monoclonal antibody (Mab) rituximab or Ruxience to Moxetumomab pasudotox-tdfk.
-To determine the safety and toxicity of Moxetumomab pasudotox-tdfk and rituximab/Ruxience
used at the planned dose level, in patients with HCL and HCLv.
HCL or HCLv with at least 1 prior purine analog, and, for HCL patients with >=2-years 1
month response, at least 1 other therapy.
Need for treatment, either 1) ANC <1/nL, 2) Hgb <10g/dL, 3) Plt <100/nL, 4) symptomatic
splenomegaly, or enlarging HCL mass > 2cm in short axis
Serum creatinine < 1.5 mg/dL, or creatinine clearance greater than or equal to 60 mL/min
by Cockcroft-Gault equation, where creatinine clearance = (140-age)(kg weight)/(72 x
No uncontrolled infection or cardiopulmonary dysfunction
Phase I trial, two arm, non-randomized, dose escalation
Patients 1-13: Moxetumomab pasudotox-tdfk 30-40 mcg/kg intravenous (iv) over 30
min, Rituximab 375 mg/m^2 iv, 50-400 mg/hr.
Patients 14-26: Moxetumomab pasudotox-tdfk 40 mcg/kg intravenous (iv) over 30 min,
Ruxience 375 mg/m2 iv, 50-400 mg/hr
Rituximab or Ruxience day 1 (begin day -2 on cycle 1), Moxetumomab pasudotox-tdfk
days 1, 3, and 5.
Patients will receive up 4 cycles past documentation of CR without MRD, maximum 8.
To prevent renal toxicity and hypovolemia, patients will be encouraged to drink
water gradually, approximately 0.5-1 cup/hour or 6L/day, not going >3 hours without
drinking from days 1 to 8 and to keep a hydration diary to record daily fluid
To prevent rituximab/Ruxience toxicity, patients will receive prophylactic
dexamethasone orally 0.5- 2 hours before the 1st dose of rituximab, and before
subsequent doses until rituximab/Ruxience infusion reactions are not seen. Patients
will also receive diphenhydramine, famotidine, and acetaminophen.
Dexamethasone 4 mg orally (maximum 2 doses/day) will be given as needed to treat
nausea or fever associated with Moxetumomab pasudotox-tdfk, which might prevent
adequate water intake
Up to 26 patients are intended to be treated in the trial. While a total of 26
evaluable patients will be enrolled, the accrual ceiling will be set at 30 to
include screen failures and inevaluable patients.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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