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Arm 1 Moxetumomab Pasudotox-tdfk + Rituximab

Arm 1 and Arm 2 Moxetumomab Pasudotox-tdfk + Ruxience

Moxetumomab pasudotox-tdfk is administered at 30-40 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Moxetumomab Pasudotox-tdfk

Rituximab will be administered at 375mg/m\^2 intravenous (iv), 50-400 mg/hour (hr). On cycle 1, Rituximab is given on day -2, on subsequent cycles, Rituximab is given on day 1.

Ruxience will be administered at 375mg/m\^2 intravenous (iv), 50-400 mg/hour (hr). On cycle 1, Ruxience is given on day -2, on subsequent cycles, Ruxience is given on day 1 (Delta)

Ruxience

12 mg Cycle 1, Day -2; Cycles 2-8, Day 1. Administer 0.5-2 hours before rituximab/Ruxience. If participant has previous reaction to rituximab/Ruxience, give 12mg. If participants tolerate rituximab/Ruxience without problems, may hold at discretion of provider. Pre-medications are given prior to rituximab/Ruxience on day 1.

650 mg Cycle 1, Day -2, Day 1, Day 3, Day 5. To be given 30-90 minutes prior to every moxetumomab pasudotox-tdfk infusion and recommended every 6 hours x 4 after the end of infusion; Cycles 2-8, Day 1, Day 3, Day 5. To be given 30-90 minutes prior to every moxetumomab pasudotox-tdfk infusion and recommended every 6 hours x 4 after the end of infusion. Pre-medications are given prior to rituximab/Ruxience on day 1.

25-50 mg Cycle 1, Day -2; Cycles 2-8, Day 1. Pre-medications are given prior to rituximab/Ruxience on day 1. May be given prior to moxetumomab pasudotox-tdfk at discretion of principal investigator.

20-40 mg Cycle 1, Day -2; Day 1, Day 3, Day 5. To be given 30-90 minutes prior to every moxetumomab pasudotox-tdfk infusion and is recommended every 12 hours x 2 after the end of infusion; Cycles 2-8, Day 1, Day 3, Day 5. To be given 30-90 minutes prior to every moxetumomab pasudotox-tdfk infusion and is recommended every 12 hours x 2 after the end of infusion. Pre-medications are given prior to rituximab/Ruxience on day 1.

81 mg Cycle 1, Days 1-8; Cycles 2-8, Days 1-8. Only if platelet counts ≥ 100 x 109/L.

Robert J Kreitman, M.D.

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.

...

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.

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

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

All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Dose limiting toxicity (DLT) is defined as all treatment related Grade 3-5 adverse events (AEs) occurring from the initiation of moxetumomab pasudotox-tdfk therapy to within 30 days after the last dose of moxetumomab pasudotox-tdfk treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Recommended safe dose of moxetumomab pasudotox-tdfk is defined as the treatment of 10 participants with no more than 2 experiencing a dose-limiting toxicity (DLT). A DLT is defined as all treatment related Grade 3-5 adverse events (AEs) occurring from the initiation of moxetumomab pasudotox-tdfk therapy to within 30 days after the last dose of moxetumomab pasudotox-tdfk treatment assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Recommended safe dose of rituximab/Ruxience is defined as the treatment of 10 participants with no more than 2 experiencing a dose-limiting toxicity (DLT). A DLT is defined as all treatment related Grade 3-5 adverse events (AEs) occurring from the initiation of moxetumomab pasudotox-tdfk therapy to within 30 days after the last dose of moxetumomab pasudotox-tdfk treatment assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Number of participants whose cancer shrinks or disappears after treatment defined as minimal residual disease. MRD is no hairy cell leukemia (HCL) in the blood and bone marrow aspirate flow determined by immunohistochemistry (IHC) and flow cytometry of blood and bone marrow aspirate.

MRD-free is defined as participants with no hairy cell leukemia (HCL) in the blood and bone marrow aspirate flow determined by immunohistochemistry (IHC) and flow cytometry of blood and bone marrow aspirate.

DOR is defined as the time of initial response until documented tumor progression. Response was assessed by the and is defined as an increase in symptoms or \>25% decline in hematologic parameters related to disease, based on the judgement of the principal investigator. ≥50% increase in sum of products of perpendicular diameters of evaluable (\> 2cm) lymphadenopathy or appearance of new evaluable lymph nodes \> 2 cm short axis.

National Cancer Institute (NCI)

Principal Investigator

Participants with Relapsed/Refractory Hairy Cell Leukemia (HCL) or Hairy Cell Leukemia (HCLv)

Arm 1 Moxetumomab Pasudotox-tdfk + Rituximab

Dose escalation treatment with moxetumomab -pasudotox-tdfk and rituximab Moxetumomab pasudotox-tdfk is administered at 30 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Rituximab will be administered at 375mg/m\^2 iv, 50-400 mg/hour (hr). On cycle 1, Rituximab is given on day -2, on subsequent cycles, Rituximab is given on day 1.

Moxetumomab - Dose Escalation 30 mcg/kg

Dose expansion; treatment with moxetumomab -pasudotox-tdfk and Ruxience

Arm 1 and Arm 2 Moxetumomab Pasudotox-tdfk + Ruxience

Moxetumomab pasudotox-tdfk is administered at 40 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Ruxience will be administered at 375mg/m\^2 iv, 50-400 mg/hour (hr). On cycle 1, Ruxience is given on day -2, on subsequent cycles, Ruxience is given on day 1 (Delta)

Moxetumomab - Dose Expansion 40 mcg/kg

Participants with Relapsed/Refractory Hairy Cell Leukemia (HCL) or Hairy Cell Leukemia (HCLv)

Arm 1 Moxetumomab Pasudotox-tdfk + Rituximab

Dose escalation treatment with moxetumomab -pasudotox-tdfk and rituximab Moxetumomab pasudotox-tdfk is administered at 30-40 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Rituximab will be administered at 375mg/m\^2 iv, 50-400 mg/hour (hr). On cycle 1, Rituximab is given on day -2, on subsequent cycles, Rituximab is given on day 1.

Dose expansion; treatment with moxetumomab -pasudotox-tdfk and Ruxience

Arm 1 and Arm 2 Moxetumomab Pasudotox-tdfk + Ruxience

Moxetumomab pasudotox-tdfk is administered at 30-40 ug/Kg intravenous (iv) over 30 min given on days 1, 3, 5 of each cycle.

Ruxience will be administered at 375mg/m\^2 iv, 50-400 mg/hour (hr). On cycle 1, Ruxience is given on day -2, on subsequent cycles, Ruxience is given on day 1 (Delta)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Robert J. Kreitman

All participants in Group 1 and Group 2 who received at least one dose of Moxetumomab 30-40 mcg/kg.

Spots Global Cancer Trial Database for hcl variant

Every month we try and update this database with for hcl variant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hcl variant

Every month we try and update this database with for hcl variant cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hcl variant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.