Clinical Trials /

ADCT-602 in Treating Patients With Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia

NCT03698552

Description:

This phase I/II trial studies the side effects and best dose of ADCT-602 in treating patients with B-cell lymphoblastic leukemia that has come back or does not respond to treatment. Monoclonal antibodies, such as ADCT-602, may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: ADCT-602 in Treating Patients With Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia
  • Official Title: A Phase I/II Study to Evaluate the Safety and Anti-Tumor Activity of ADCT-602 Targeting CD22 in Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 2017-0938
  • SECONDARY ID: NCI-2018-02016
  • SECONDARY ID: 2017-0938
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03698552

Conditions

  • Blasts 5 Percent or More of Bone Marrow Nucleated Cells
  • CD22 Positive
  • Philadelphia Chromosome Positive
  • Recurrent B Acute Lymphoblastic Leukemia
  • Refractory B Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
Epratuzumab-cys-tesirineADCT-602 (CN); hLL2-cys-PBD (SY); ADCT602 (CN); ADCT 602 (CN); hLL2-cys-SG3249 (SY); Epratuzumab-cys-SG3249 (SY) ; ADC ADCT-602Treatment (epratuzumab-cys-tesirine)

Purpose

This phase I/II trial studies the side effects and best dose of ADCT-602 in treating patients with B-cell lymphoblastic leukemia that has come back or does not respond to treatment. Monoclonal antibodies, such as ADCT-602, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluate the safety and determine the maximum tolerated dose (MTD) of
      epratuzumab-cys-tesirine (ADCT-602) in patients with relapsed or refractory B-cell (B)-acute
      lymphoblastic leukemia (ALL) in Phase 1.

      II. Determine the recommended dose of ADCT-602 for Phase 2. III. Evaluate the efficacy
      (complete response [CR] with incomplete marrow recovery [CR/CRi] rate) of ADCT-602 in Phase
      2.

      SECONDARY OBJECTIVES:

      I. Evaluate the clinical activity of ADCT-602, based on duration of response (DOR), overall
      survival (OS), and progression-free survival (PFS).

      II. Characterize the pharmacokinetic (PK) profile of ADCT-602. III. Evaluate the
      immunogenicity of ADCT-602. IV. Characterize the effect of ADCT-602 exposure on the QT
      interval.

      EXPLORATORY OBJECTIVES:

      I. Obtain preliminary data on the correlation between the clinical activity and PK profile of
      ADCT-602 with the baseline expression of CD22 and other cluster of differentiation (CD)
      markers in peripheral blood.

      II. Assess the impact of soluble CD22 (sCD22) on ADCT-602 PK.

      OUTLINE: This is a dose escalation study followed by a phase II study.

      Patients receive epratuzumab-cys-tesirine intravenously (IV) over 30 minutes on day 1.
      Courses repeat every 21 in the absence of disease progression or unacceptable toxicity.
      Patients who achieve CR/CRi receive epratuzumab-cys-tesirine every 28 days.

      After completion of study treatment, patients are followed up at 30 days and then every 12
      weeks for up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (epratuzumab-cys-tesirine)ExperimentalPatients receive epratuzumab-cys-tesirine IV over 30 minutes on day 1. Courses repeat every 21 in the absence of disease progression or unacceptable toxicity. Patients who achieve CR/CRi receive epratuzumab-cys-tesirine every 28 days.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients with relapsed or refractory B-ALL. Philadelphia chromosome positive (Ph+) ALL
                 is allowed after failing either first or second generation tyrosine kinase inhibitor.
                 Note: Patients in first relapse with complete remission (CR1) duration > 12 months are
                 excluded
    
              -  Expression of CD22 in >= 20% blasts (assessed by flow-cytometry or
                 immunohistochemistry)
    
              -  Marrow blast count >= 5%
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2
    
              -  Serum creatinine =< 1.5 mg/dL. If the patient has a creatinine > 1.5 mg/dL, creatinine
                 clearance must be > 60 mL/min/1.73 m^2, as calculated by the Cockcroft and Gault
                 equation, or modification of diet in renal disease (MDRD) formula or 24-hour urine
                 analysis
    
              -  Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2 times
                 the upper limit of normal (ULN); =< 5 times ULN if there is liver or bone involvement
    
              -  Total bilirubin =< 1.5 times ULN. Patients with known Gilbert's syndrome may have a
                 total bilirubin up to =< 3 times ULN.
    
                   -  NOTE: In patients (pts) with elevated total bilirubin due to increased indirect
                      bilirubin, patients with direct bilirubin =< 1.5 x ULN are eligible
    
              -  Left ventricular ejection fraction (LVEF) >= 45%
    
              -  Negative urine or serum beta-human chorionic gonadotropin (B-HCG) pregnancy test
                 within 7 days prior to the cycle 1, day 1 visit, for women of child-bearing potential.
                 Women of child bearing potential must agree to use an effective method of
                 contraception from the time of giving informed consent until at least 16 weeks after
                 the last dose of ADCT-602. Men with female partners who are of child bearing potential
                 must agree that they or their partners will use a highly effective method of
                 contraception from the time of giving informed consent until at least 16 weeks after
                 the patient receives his last dose of ADCT-602
    
                   -  Women of child bearing potential defined as: Sexually mature women who have not
                      undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or
                      who have not been postmenopausal (i.e., who have not menstruated at all) for at
                      least 1 year
    
                   -  Effective method of contraception defined as: Hormonal contraceptives (oral,
                      injectable, patch, intrauterine devices), male partner sterilization, or total
                      abstinence from heterosexual intercourse, when this is the preferred and usual
                      lifestyle of the patient
    
                        -  NOTE: The double-barrier method (e.g., synthetic condoms, diaphragm, or
                           cervical cap with spermicidal foam, cream, or gel), periodic abstinence
                           (such as calendar, symptothermal, post ovulation), withdrawal (coitus
                           interruptus), lactational amenorrhea method, and spermicide-only are not
                           acceptable as highly effective methods of contraception
    
              -  White blood cell (WBC) value of < 15,000 cells/uL prior to cycle 1 day 1
    
            Exclusion Criteria:
    
              -  Known active central nervous system (CNS) leukemia, defined as morphologic evidence of
                 lymphoblasts in the cerebrospinal fluid (CSF), or symptomatic CNS leukemia (i.e.,
                 cranial nerve palsies or other significant neurologic dysfunction) within 28 days
                 prior to screening.
    
                   -  NOTE: Patients may have a history of CNS leukemic involvement if they have
                      received prior treatment for CNS involvement and no evidence of active disease
                      (defined as >= 2 consecutive spinal fluid assessments with no evidence of
                      disease) is present at screening. Prophylactic intrathecal chemotherapy is
                      allowed on the trial and is not a criterion for exclusion
    
              -  Patients with Burkitt's leukemia/lymphoma
    
              -  Active graft-versus-host disease (GVHD) or severe/extensive chronic GVHD
    
              -  Autologous or allogenic transplant within the 60 days prior to the cycle 1 day1
    
              -  Known history of immunogenicity or hypersensitivity to a CD22 antibody
    
              -  Known history of positive serum human adenosine deaminase (ADA)
    
              -  Known seropositive for human immunodeficiency (HIV), hepatitis B, or hepatitis C virus
                 with confirmatory testing
    
              -  History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome
    
              -  Pregnant or breastfeeding women
    
              -  Significant medical comorbidities, including uncontrolled hypertension (diastolic
                 blood pressure > 115 mm Hg), uncontrolled atrial or ventricular cardiac arrhythmias,
                 unstable angina, congestive heart failure (greater than New York Heart Association
                 class II), severe uncontrolled ventricular arrhythmias, electrocardiographic evidence
                 of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease,
                 coronary angioplasty, myocardial infarction within 6 months prior to screening
    
              -  Use of any other experimental medication(s) within 14 days or 5 half-lives, but in no
                 case < 14 days prior to the start of study treatment on cycle 1, day 1
    
              -  Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea, steroids and any
                 targeted small molecules or biologics), or radiotherapy within 14 days or 5 half-lives
                 (whichever is shorter) prior to cycle 1, day 1 treatment
    
                   -  NOTE: a) To reduce the circulating lymphoblast count or palliation: steroids and
                      hydroxyurea are allowed. No washout necessary for these agents. b) Cytarabine IV
                      could be used for cytoreduction with a washout of 1 week. c) For ALL
                      maintenance/treatment: mercaptopurine, oral methotrexate, vincristine, and/or
                      tyrosine kinase inhibitors. These agents should be discontinued at least 48 hours
                      prior to start of study drugs. d) Patients may have received prior CD22-directed
                      therapy provided the blasts remain CD22+ (>= 20%) and > 3 months from prior
                      anti-CD22 exposure
    
              -  Isolated extramedullary relapse (i.e., testicular, CNS)
    
              -  Uncontrolled active infection
    
              -  History of another primary invasive malignancy that has not been definitively treated
                 or in remission for less than 2 years. Patients with non-melanoma skin cancers or with
                 carcinomas in situ are eligible regardless of the time from diagnosis (including
                 concomitant diagnoses)
    
              -  Any other significant medical illness, abnormality, or condition that would, in the
                 Investigator's judgment, make the patient inappropriate for study participation or put
                 the patient at risk
    
              -  Inability of the patient to consent themselves for this study
    
              -  Prior history or current veno-occlusive disease (VOD)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Maximum tolerated dose (MTD) as determined by dose limiting toxicities (DLTs) (Phase I)
    Time Frame:Up to 21 days
    Safety Issue:
    Description:The MTD is the highest dose level in which the study has treated 6 patients with at most 1 experiencing the DLT. The 3+3 algorithm along with DLTs observed during the first 21 days of the first treatment cycle will be used to guide dose escalation/de-escalation.

    Secondary Outcome Measures

    Measure:Overall response rate (ORR)
    Time Frame:Up to 1 year
    Safety Issue:
    Description:
    Measure:Overall survival (OS)
    Time Frame:Up to 1 year
    Safety Issue:
    Description:
    Measure:Progression-free survival (PFS)
    Time Frame:Up to 1 year
    Safety Issue:
    Description:
    Measure:Measure the amount of Epratuzumab-cys-tesirine in the body at different time points.
    Time Frame:Up to 1 year
    Safety Issue:
    Description:Blood for testing the amount of Epratuzumab-cys-tesirine in the body at different time points drawn 4 times over the 6 hours after the dose.
    Measure:Epratuzumab-cys-tesirine exposure on QT interval assessed by EKG
    Time Frame:Baseline up to 30 days after study drug stopped
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:M.D. Anderson Cancer Center

    Last Updated