Moxetumomab Pasudotox-tdfk (Lumoxiti(TM)) and Either Rituximab (Rituxan(R)) or Ruxience for Relapsed Hairy Cell Leukemia

Hairy Cell Leukemia Clinical Trial

Official title: A Phase I Study of Moxetumomab Pasudotox-tdfk (Lumoxiti (TM)) and Either Rituximab (Rituxan (R)) or Ruxience for Relapsed Hairy Cell Leukemia

Status Active, not recruiting

Clinical Trial Summary

Background:

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 better.

Objective:

To test the safety of Moxetumomab pasudotox taken with Rituximab/Ruxience for people with HCL or HCL variant.

Eligibility:

People age 18 years and older with HCL or HCL variant that has not responded to standard therapy

Design:

Participants will be screened with:

Medical history

Physical exam

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.

Scans

Exercise test

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:

1. visit to get Rituximab/Ruxience for 2-4 hours and Lumoxiti for 30 minutes

2. 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.

...

Clinical Trial Description

Background:

• Hairy cell leukemia (HCL) is an indolent cluster of differentiation-22 (CD22+) B-cell leukemia comprising 2% of all leukemias, or approximately 1200 of the 62,130 new cases of leukemia/year in the United States (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. hairy cell leukemia variant (HCL-V) cells are cluster of Differentiation 25 (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 (Immunoglobulin Heavy Variable 4-34) 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 complete response (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-cluster of differentiation 20 (CD20) monoclonal antibody (Mab) rituximab or Ruxience to Moxetumomab pasudotox-tdfk.

Objective:

-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.

Eligibility:

• 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) absolute neutrophil count (ANC) <1/nL, 2) hemoglobin (Hgb) <10g/dL, 3) platelet (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 Creatinine).

• No uncontrolled infection or cardiopulmonary dysfunction

Design:

• Phase I trial, two arm, non-randomized, dose escalation

• Administration:

• 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 to 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 consumption.

• 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

• Statistical design:

• 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. ;

Related Conditions & MeSH terms

• Hairy Cell Leukemia
• Leukemia
• Leukemia, Hairy Cell

• NCT number: NCT03805932
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 3, 2019
• Completion date: June 30, 2025