NCT02338050

Brief Summary

This is a phase II, open-label, nonrandomized, prospective study to evaluate the activity, safety, and feasibility of administration of moxetumomab pasudotox in the pre-allogeneic hematopoietic cell transplantation (HCT) setting to patients with B-lineage Acute Lymphoblastic Leukemia (ALL) who are in a morphologic complete remission and have pre-transplant minimal residual disease (MRD) \> 0.01% (detected by flow cytometry). The primary objective of this study is to determine if treatment with moxetumomab pasudotox in the MRD positive setting is able to lead to MRD negativity (\< 0.01% by flow cytometry) or at least a 1-log10 reduction in MRD prior to allogeneic HCT.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1

participants targeted

Target at below P25 for phase_2

Geographic Reach
1 country

4 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 6, 2015

Completed
8 days until next milestone

First Posted

Study publicly available on registry

January 14, 2015

Completed
4 months until next milestone

Study Start

First participant enrolled

May 1, 2015

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2020

Completed
Last Updated

September 16, 2015

Status Verified

September 1, 2015

Enrollment Period

5 years

First QC Date

January 6, 2015

Last Update Submit

September 15, 2015

Conditions

Acute Lymphoblastic Leukemia (ALL)

Keywords

ALLMoxetumomab PasudotoxMoxeCAT-8015, HA22

Outcome Measures

Primary Outcomes (1)

  • MRD negativity

    The primary endpoint is the event of whether patients successfully achieved either MRD negativity (defined as \<0.01%) or at least 1 log10 reduction in MRD levels using flow cytometry via central laboratory testing after moxetumomab treatment but prior to HCT relative to pre-moxetumomab MRD measurement (baseline). The proportion of patients who become MRD negative or who have at least a 1-log10 reduction from baseline will be summarized and 80% confidence intervals will provided. An exploratory analysis of the association between CD22 expression at eligibility and the response rate will also be conducted.

    change in MRD levels between baseline and 3-10 days post last Moxe dose

Secondary Outcomes (11)

  • MRD level and its log reduction from baseline

    baseline and 3-10 days post last Moxe dose

  • Overall Survival (OS)

    from Moxe Dose 1 through date of death from any cause (assessed through 2 years post HCT or last Moxe dose)

  • Progression-free survival (PFS)

    from Moxe Dose 1 through date of progression or death from any cause (assessed through 2 years post HCT or last Moxe dose)

  • Proportion of patients proceeding to transplant

    from Moxe Dose 1 through Day 0 of transplant

  • Relapse

    from Moxe Dose 1 through date of relapse (assessed through 2 years post HCT or last Moxe dose)

  • +6 more secondary outcomes

Study Arms (1)

Moxetumomab Pasudotox

EXPERIMENTAL

Moxetumomab pasudotox 32 mcg/kg/dose IV every other day for a total of 6 doses. Dexamethasone 2.5 mg/m2/dose (or corticosteroid equivalent) will be administered before and after each dose of moxetumomab pasudotox.

Biological: Moxetumomab Pasudotox

Interventions

Moxetumomab PasudotoxBIOLOGICAL
Also known as: (CAT-8015, HA22)
Moxetumomab Pasudotox

Eligibility Criteria

Age6 Months - 24 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • ≥ 6 months and \< 25 years of age
  • Histologically confirmed diagnosis of B-lineage ALL. Verification of CD22 expression is not required
  • Bone marrow in morphologic remission (any remission number) defined as \< 5% blasts (M1 classification) performed in local institution lab
  • CNS 1 (\< 5/μL WBCs in CSF and cytospin negative for blasts)
  • Evidence of bone marrow MRD defined as ≥ 0.01% by flow cytometry performed in the study central lab
  • Candidate committed to HCT independent of participation in this study, with the following requirements:
  • Meets local transplant center eligibility requirements for HCT
  • In the opinion of the HCT center will be ready to begin pre-transplant conditioning within 6 weeks of trial enrollment from a medical and psychosocial standpoint
  • Has an available HCT donor or identified cord blood unit. Related and unrelated donors, and bone marrow, peripheral blood, or cord blood stem cell sources allowed
  • Adequate organ function including the following:
  • Hepatic function: Total bilirubin \< 1.5 × upper limit of normal (ULN) (except in the case of subjects with known Gilbert's disease: \< 5 × ULN) and transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) \< 3 × ULN based on age- and institution specific laboratory-specific normal ranges
  • Renal function: Age-adjusted normal serum creatinine is required. A 24-hour creatinine clearance value \> 60 mL/min/1.73 m2 (updated Schwartz formula or nuclear GFR) must be obtained if serum creatinine is elevated.
  • Hematologic function: Absolute neutrophil count (ANC) \> 500/μL and platelet count \> 25,000/μL without transfusion
  • Oxygen saturation at rest or with exercise \> 88% as measured by pulse oximeter or PaO2 \> 55 mm Hg without need for supplemental oxygen at rest or with activity
  • Serum albumin \> 2 g/dL
  • +6 more criteria

You may not qualify if:

  • Active extramedullary disease at any site. (Note: Definitive therapy of known previous sites of extramedullary disease is allowed)
  • Females who are breast-feeding or pregnant
  • Subjects with known 11q23 MLL rearrangement are excluded.
  • Prior therapy:
  • Prior treatment with CAT-3888 (BL22), moxetumomab pasudotox (CAT-8015, HA22), any pseudomonas-exotoxin-containing compound, or any anti-CD22 directed therapy at any time in the past
  • Prior allogeneic or autologous HCT or adoptive cellular therapies, including T-cell chimeric antigen receptor (CAR) therapy
  • Chemotherapy \< 2 weeks prior to starting study drug with the following exception: There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such
  • Monoclonal antibody therapy \< 30 days from study enrollment
  • Other investigational agents currently or within 30 days prior to study enrollment
  • Subjects with an absolute contraindication to corticosteroid administration
  • HIV infection (due to increased risk of severe infection and unknown interaction of moxetumomab pasudotox with antiretroviral drugs)
  • Active hepatitis B or C infection as defined by seropositivity for hepatitis B (hepatitis B surface antigen \[HbsAg\]) or hepatitis C (hepatitis C antibody) and elevated liver transaminases (defined as above the ULN per the institution normal ranges)
  • Second malignancy other than non-basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and subject is in remission
  • Subject with clinical or laboratory evidence of active DIC
  • Subject with prior history of thrombotic microangiopathy or HUS within 3 months prior to enrollment
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Childrens Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

  • Shah NN, Schneiderman J, Kuruvilla D, Bhojwani D, Fry TJ, Martin PL, Schultz KR, Silverman LB, Whitlock JA, Wood B, Vainshtein I, Adams A, Confer D, Pulsipher MA, Chaudhury S, Wayne AS. Fatal capillary leak syndrome in a child with acute lymphoblastic leukemia treated with moxetumomab pasudotox for pre-transplant minimal residual disease reduction. Pediatr Blood Cancer. 2021 Jan;68(1):e28574. doi: 10.1002/pbc.28574. Epub 2020 Sep 22. No abstract available.

    PMID: 32959985DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

immunotoxin HA22HA 22

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Alan S Wayne, MD

    Children's Hospital Los Angeles

    STUDY CHAIR

  • Nirali N Shah, MD

    National Institutes of Health (NIH)

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 6, 2015

First Posted

January 14, 2015

Study Start

May 1, 2015

Primary Completion

May 1, 2020

Last Updated

September 16, 2015

Record last verified: 2015-09

Locations

US(4)