Study of Moxetumomab Pasudotox in Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)

NCT01891981 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 2012-1143NCI-2013-02207
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of moxetumomab pasudotox that can be given to patients with relapsed and/or refractory ALL.

Conditions

Leukemia

Keywords

Leukemia; Acute Lymphoblastic Leukemia; ALL; Relapsed and/or refractory; Moxetumomab Pasudotox; Maximum tolerated dose; MTD

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Moxetumomab

  Maximum tolerated dose defined as the highest dose level in which 6 patients have been evaluated for toxicity and fewer than 2 dose limiting toxicities (DLTs) were observed. A non-hematologic DLT defined as a clinically significant Grade 3 or 4 adverse event or abnormal laboratory value assessed by treating physician as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during the first 21(+/- 2) days on study. A hematologic dose-limiting toxicity defined as severe myelosuppression with a hypoplastic marrow with less than 5% cellularity and no evidence of leukemia 42 days from start of therapy.

  After second 21 day cycle

Secondary Outcomes (1)

• Overall Response Rate

  After second 21 day cycle

Study Arms (1)

Moxetumomab Pasudotox

EXPERIMENTAL

Phase I Starting Dose: 30 µg/kg by vein every other day for 6 doses on Days 1, 3, 5, 7, 9, and 11 of each 21-day cycle. Phase II Starting Dose: Maximum tolerated dose from Phase I.

Drug: Moxetumomab Pasudotox

Interventions

Moxetumomab Pasudotox DRUG

Phase I Starting Dose: 30 µg/kg by vein every other day for 6 doses on Days 1, 3, 5, 7, 9, and 11 of each 21-day cycle. Phase II Starting Dose: Maximum tolerated dose from Phase I.

Moxetumomab Pasudotox

Eligibility Criteria

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

You may qualify if:

• Patients age 18 years or older with previously treated ALL (relapsed and/or refractory after prior therapy); patients with relapsed/refractory biphenotypic leukemia expressing the appropriate antigen (CD22) are also eligible to participate, Pediatric patients younger than 18 may be considered with sponsor approval once the MTD has been established in the adult population.
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
• Adequate liver function (bilirubin less than or equal to 1.5 mg/dL and serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) less than or equal 2.5 x upper limit of normal (ULN), unless considered due to tumor or hemolysis), and renal function ( Calculated CrCl of greater than or equal to 50 or serum creatinine less than 2 x ULN.) Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is less than or equal to 2.0 mg/dL (unless due to hemolysis or Gilbert's disease, i.e. mainly indirect bilirubin) and creatinine less than or equal 2 mg/dL
• Provision of written informed consent.

You may not qualify if:

• Patient with active heart disease (NYHA class greater than or equal to 2 as assessed by history and physical examination).
• Patients with a cardiac ejection fraction (as measured by either multigated radionuclide angiography (MUGA) or echocardiogram) less than 40%
• Patients with active hepatitis
• Pregnant or breast-feeding women. Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of start of treatment.
• prior radioimmunotherapy within 3 years of enrollment
• serum albumin less than 2g/dL
• oxygen saturation at rest by pulse oximetry less than 88% or PaO2 less than or equal to 55mm Hg
• history of microangiopathic hemolysis, TTP or HUS.
• symptomatic central nervous system (CNS) involvement
• Less than 100 days post -transplant or any evidence of active graft-versus-host disease (GVHD)
• systemic chemotherapy less than 14 days prior; however treatment may start earlier if there is evidence of rapidly progressive disease if approved by the Principal Investigator
• monoclonal antibody therapy less than 1 month
• investigational agents within 28 days of dosing; however treatment may start earlier if there is evidence of rapidly progressive disease if approved by the Principal Investigator
• HIV+/AIDS
• history of exposure to pseudomonas exotoxin containing molecule

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• MedImmune LLC: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Muller F, Cunningham T, Stookey S, Tai CH, Burkett S, Jailwala P, Stetler Stevenson M, Cam MC, Wayne AS, Pastan I. 5-Azacytidine prevents relapse and produces long-term complete remissions in leukemia xenografts treated with Moxetumomab pasudotox. Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1867-E1875. doi: 10.1073/pnas.1714512115. Epub 2018 Feb 5.

  PMID: 29432154 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

immunotoxin HA22

Condition Hierarchy (Ancestors)

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

Study Officials

• Farhad Ravandi-Kashani, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2013
• First Posted: July 3, 2013
• Study Start: December 17, 2013
• Primary Completion: April 12, 2017
• Study Completion: April 12, 2017
• Last Updated: October 13, 2023

Record last verified: 2023-10

Locations

US (1)