Clinical Trials / Research Studies

Clinical Trials / Research Studies

AALL1621: A Phase 2 Study of Inotuzumab Ozogamicin (NSC# 772518) in Children and Young Adults With Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL)

Why are we doing this research?

PURPOSE:

This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with CD22 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. Immunotoxins, such as inotuzumab ozogamicin, are antibodies linked to a toxic substance and may help find cancer cells that express CD22 and kill them without harming normal cells.


DETAILED DESCRIPTION:

PRIMARY OBJECTIVES:

  • To determine the morphologic response rate (complete response [CR] + complete response with incomplete hematologic recovery [CRi]) following one cycle of treatment with inotuzumab ozogamicin (InO) in children with relapsed or refractory CD22+ B acute lymphoblastic leukemia (B-ALL).

SECONDARY OBJECTIVES:

  • To determine the CR/CRi rate following 2 cycles of InO therapy.
  • To determine the safety of single agent InO administered at the adult recommended phase 2 dose (RP2D) to pediatric patients with relapsed or refractory CD22+ B-ALL.
  • To determine the level of minimal residual disease (MRD) by flow cytometry in responding patients.
  • To determine the incidence, severity, and outcomes of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) of the liver in patients during InO therapy and following subsequent treatment, including myeloablative hematopoietic stem cell transplantation (HSCT).
  • To estimate the 3-year event-free survival (EFS), 3-year overall survival (OS), and among responders duration of CR/CRi for pediatric patients with relapsed or refractory B-ALL treated with InO.

Study Type: Interventional

Intervention Model: Single Group Assignment


Masking: No masking


Primary Purpose: Treatment

Who can participate?

AGES ELIGIBLE FOR STUDY: 1 year to 21 Years

ELIGIBILITY CRITERIA

Inclusion Criteria:

  • Patients must have B-ALL with >= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
  • Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a phycoerythrin [PE] fluorophore is strongly recommended)
  • In the case of an inadequate aspirate sample (dry tap), flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
  • Patient must have one of the following:
  • Second or greater relapse;
  • Primary refractory disease with at least 2 prior induction attempts;
  • First or greater relapse refractory to at least one prior re-induction attempt
  • Relapsed patients previously diagnosed with B-lymphoblastic lymphoma are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
  • Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study

Exclusion Criteria:

  • Patients with any prior history of SOS/VOD irrespective of severity
  • Patients with isolated central nervous system (CNS), testicular, or other extramedullary site of relapse
  • Patients who have been previously treated with InO
  • Patients with active optic nerve and/or retinal involvement that would require urgent radiation therapy concurrent with protocol therapy; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
  • Patients who are currently receiving another investigational drug
  • Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy and intrathecal chemotherapy)
  • Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD medications (meds)
  • Patients who are currently receiving or plan to receive corticosteroids except as described below
    • Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, as a premedication for InO and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications
  • Patients who have an active uncontrolled infection defined as:
    • Positive bacterial blood culture within 48 hours of study enrollment;
    • Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with clinical signs of infection; fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
    • A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
    • Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved; for patients with clostridium (c.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
    • Active viral or protozoal infection requiring IV treatment
  • Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections; testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient
  • Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome
  • Women of childbearing potential should be advised to avoid becoming pregnant while receiving InO; women should not breast-feed during treatment with InO and for at least 3 months after the final dose
    • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days of starting protocol therapy
    • Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of InO
    • Men with female partners of childbearing potential should use effective contraception during treatment with InO and for at least 5 months after the last dose of InO
    • Lactating females are not eligible unless they agree not to breastfeed their infants
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study

Conditions

  • Leukemia ALL Relapse - Refractory
  • Adult - Leukemia ALL Relapse - Refractory

Contact

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave.
Cincinnati OH 45229-3039

Phone: 513-636-2799
cancer@cchmc.org