ClinicalTrials.gov
ClinicalTrials.gov Menu

Inotuzumab Ozogamicin in Treating Younger Patients With Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02981628
Recruitment Status : Active, not recruiting
First Posted : December 5, 2016
Last Update Posted : December 26, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Childhood B Acute Lymphoblastic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Refractory Childhood Acute Lymphoblastic Leukemia Biological: Inotuzumab Ozogamicin Other: Laboratory Biomarker Analysis Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. To determine the CR/CRi rate following 2 cycles of InO therapy.

II. 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.

III. To determine the level of minimal residual disease (MRD) by flow cytometry in responding patients.

IV. 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).

V. 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.

OUTLINE:

Patients receive inotuzumab ozogamicin intravenously (IV) over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then yearly for 4 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : June 5, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: Treatment (inotuzumab ozogamicin)
Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Biological: Inotuzumab Ozogamicin
Given IV
Other Names:
  • CMC-544
  • Way 207294
  • WAY-207294

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Morphologic response (CR + CRi) [ Time Frame: Up to 28 days ]
    The response rate will be estimated as the percent of eligible and evaluable responders (CR/CRi). A one-sided lower 95% Agresti-Coull confidence limit will be calculated.


Secondary Outcome Measures :
  1. Duration of CR/CRi [ Time Frame: Up to 3 years ]
    Among responding patients, three-year complete continuous response will also be estimated using duration of CR/CRi for the overall responding group and stratified by whether or not the patients proceed to HSCT.

  2. EFS [ Time Frame: From study entry to first event (induction failure, induction death, relapse, second malignancy, remission death), or date of last follow-up, assessed at 3 years ]
    Standard errors and confidence intervals for EFS will be calculated using Peto's method.

  3. Incidence of adverse events of SOS/VOD of liver evaluated according to NCI CTCAE version 5.0 [ Time Frame: Up to 5 years ]
    The incidence, severity, and outcomes of SOS/VOD of the liver in patients during InO therapy and following subsequent treatment including myeloablative HSCT will be described. Safety monitoring (for VOD/SOS) will be performed using Pocock continuous stopping bounds.

  4. Incidence of dose-limiting toxicities at RP2D evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 42 days ]
    Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. For a given reporting period, a patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Safety monitoring (for DLT) will be performed using Pocock continuous stopping bounds.

  5. Level of MRD assessed in bone marrow by flow cytometry [ Time Frame: Up to 5 years ]
    MRD negativity rates (< 0.01% detectable leukemia cells) will be estimated.

  6. Morphologic response (CR + CRi) [ Time Frame: Up to 56 days ]
    The response rate will be estimated as the percent of eligible and evaluable responders (CR/CRi). A one-sided lower 95% Agresti-Coull confidence limit will be calculated.

  7. OS [ Time Frame: From study entry to death or date of last follow-up, assessed at 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

    • Myelosuppressive chemotherapy:

      • Patients who relapse while receiving standard maintenance therapy will not be required to have a waiting period prior to enrollment onto this study; otherwise, at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exceptions of hydroxyurea or corticosteroids used for cytoreduction
      • Intrathecal cytotoxic therapy: No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone; intrathecal chemotherapy given at the time of diagnostic lumbar puncture (LP) to evaluate for relapse prior to study enrollment is allowed
    • At least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim
    • At least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
    • At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody with the exception of blinatumomab; patients must have been off blinatumomab infusion for at least 7 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria
    • >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total-body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
    • At least 90 days must have elapsed since stem cell transplant; patient must have had no more than one previous HSCT and currently have no evidence of active graft versus (vs.) host disease (GVHD)
    • At least 42 days must have elapsed since chimeric antigen receptor (CAR)-T cell therapy
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
  • A serum creatinine based on age/gender as follows:

    • 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
    • 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
    • 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
    • 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
    • 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
    • >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
  • Direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN for age

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02981628


Locations
United States, Pennsylvania
Childrens Oncology Group
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Maureen O'Brien Children's Oncology Group

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT02981628     History of Changes
Other Study ID Numbers: AALL1621
NCI-2016-01494 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AALL1621
AALL1621 ( Other Identifier: Childrens Oncology Group )
AALL1621 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
First Posted: December 5, 2016    Key Record Dates
Last Update Posted: December 26, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases