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

NCT03805932 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 19004219-C-0042
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Conditions

Hairy Cell Leukemia

Keywords

HCL Variant; Recombinant Immunotoxin; Monoclonal Antibody; Targeted Therapy; Biologic Therapy

Outcome Measures

Primary Outcomes (2)

• Recommended Safe Dose of Moxetumomab Pasudotox-tdfk

  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.

  4 weeks

• Recommended Safe Dose of Rituximab/Ruxience

  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.

  4 weeks

Secondary Outcomes (3)

• Number of Participants Whose Cancer Shrinks or Disappears After Treatment

  28-42 days after day 1 of the last treatment.

• Number of Participants Who Are Minimal Residual Disease (MRD)-Free

  28-42 days after day 1 of the last treatment.

• Duration of Response (DOR)

  28-42 days after day 1 of the last treatment.

Other Outcomes (2)

• Number of Participants With a Dose-limiting Toxicity (DLT)

  From the initiation of moxetumomab pasudotox-tdfk therapy to within 30 days after the last dose

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, approximately 11 months and 13 days for the first group, and 4 months and 3 days for the second group.

Study Arms (2)

Moxetumomab - Dose Escalation 30 mcg/kg

EXPERIMENTAL

Arm 1 Moxetumomab Pasudotox-tdfk + Rituximab

Drug: Moxetumomab Pasudotox-tdfk; Biological: Rituximab; Drug: Dexamethasone; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Famotidine; Drug: Aspirin

Moxetumomab - Dose Expansion 40 mcg/kg

EXPERIMENTAL

Arm 1 and Arm 2 Moxetumomab Pasudotox-tdfk + Ruxience

Drug: Moxetumomab Pasudotox-tdfk; Biological: Ruxience; Drug: Dexamethasone; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Famotidine; Drug: Aspirin

Interventions

Moxetumomab Pasudotox-tdfk DRUG

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

Also known as: Lumoxiti

Moxetumomab - Dose Escalation 30 mcg/kg; Moxetumomab - Dose Expansion 40 mcg/kg

Rituximab BIOLOGICAL

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.

Also known as: Rituxan

Moxetumomab - Dose Escalation 30 mcg/kg

Ruxience BIOLOGICAL

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)

Also known as: Rituximab-pvvr

Moxetumomab - Dose Expansion 40 mcg/kg

Dexamethasone DRUG

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.

Also known as: Ozurdex, Maxidex, DexPak 6 Day

Moxetumomab - Dose Escalation 30 mcg/kg; Moxetumomab - Dose Expansion 40 mcg/kg

Acetaminophen DRUG

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.

Also known as: Tylenol, Ofirmev, FeverAll

Moxetumomab - Dose Escalation 30 mcg/kg; Moxetumomab - Dose Expansion 40 mcg/kg

Diphenhydramine DRUG

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.

Also known as: Benadryl, Nytol, Banophen

Moxetumomab - Dose Escalation 30 mcg/kg; Moxetumomab - Dose Expansion 40 mcg/kg

Famotidine DRUG

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.

Also known as: Pepcid AC, Pepcid, Acid Controller

Moxetumomab - Dose Escalation 30 mcg/kg; Moxetumomab - Dose Expansion 40 mcg/kg

Aspirin DRUG

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

Also known as: Ecotrin, Enteric Coated Aspirin, Buffered Aspirin

Moxetumomab - Dose Escalation 30 mcg/kg; Moxetumomab - Dose Expansion 40 mcg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of hairy cell leukemia (HCL) or Hairy cell leukemia variant (HCLv).
• Treatment required for either 1) Absolute neutrophil count (ANC) \<1/nL, 2) Hemoglobin \<10g/dL, 3) Platelets\<100/nL, 4) symptomatic splenomegaly, or 5) enlarging HCL mass \> 2cm in short axis. Patients who have eligible blood counts within 4 weeks from the initiation of study will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment.
• Patients must be Pseudomonas-immunotoxin naive.
• 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. Age greater than or equal to 18 years as the disease under study, HCL/HCLv, has not been reported in children \< age 18.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to2 (Karnofsky greater than or equal to 60%)
• Patients must have adequate organ and marrow function as defined below:
• Total bilirubin less than or equal to 1.5 mg/dL, unless consistent with Gilbert's (ratio between total and direct bilirubin \> 5)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3x upper limit of normal (ULN)
• Alkaline phosphatase \< 2.5 ULN
• Serum creatinine less than or equal to 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)
• Serum albumin greater than or equal to 2 g/dL
• Partial thromboplastin time (PTT) or Prothrombin time (PT)/International Normalized Ratio \< 2.5x ULN (If on warfarin, PT/INR \< 3.5x ULN; If on any other anticoagulation, Prothrombin time (PT) \< 2.5x baseline)
• Fibrinogen greater than or equal to 0.5 lower limit of normal
• The effects of moxetumomab pasudotox-tdfk and rituximab/Ruxience on the developing human fetus are unknown therefore participants must use effective methods of contraception as directed below.
• Females of childbearing potential (\< 50 years) who are sexually active with a non-sterilized male partner must use a highly effective method of contraception prior to study entry and or the duration of study participation and must agree to continue using such precautions for 12 months after completion of rituximab/Ruxience administration. Contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are premenarchal or postmenopausal (defined as 12 months with no menses without an alternative medical cause). A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Not all methods of contraception are highly effective. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Hairy Cell

Interventions

immunotoxin HA22; Rituximab; Dexamethasone; Calcium Dobesilate; Acetaminophen; Diphenhydramine; Famotidine; Aspirin

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols

Results Point of Contact

• Title: Dr. Robert J. Kreitman
• Organization: National Cancer Institute

kreitmar@mail.nih.gov

301-480-6187

Study Officials

• Robert J Kreitman, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 15, 2019
• First Posted: January 16, 2019
• Study Start: October 3, 2019
• Primary Completion: July 7, 2023
• Study Completion (Estimated): June 30, 2026
• Last Updated: July 24, 2025
• Results First Posted: November 28, 2023

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)