ADCT-602 in Treating Patients with Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia
Hematopoietic Malignancies
Leukemia
Unknown Primary
18 Years and older, Male and Female
2017-0938 (primary)
NCI-2018-02016
Summary
This phase I/II trial studies the side effects and best dose of ADCT-602 in treating patients with B-cell acute lymphoblastic leukemia that has come back (recurrent) or does not respond to treatment (refractory). Monoclonal antibodies, such as ADCT-602, may interfere with the ability of tumor cells to grow and spread.
Objectives
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 days 1, 8, and 15 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who achieve CR/CRi receive epratuzumab-cys-tesirine every 28 days.
Patients may undergo bone marrow aspirate and biopsy at screening, end of cycle 1, after cycles 2 and 3, and end of treatment.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 1 year.
Eligibility
- Male or female patients, ages 18 years and older, with relapsed or refractory B-ALL. Ph+ ALL is allowed after failing either first or second generation tyrosine kinase inhibitor. Note: Patients in first relapse with 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
Treatment Sites in Georgia
1000 Johnson Ferry Road NE
Atlanta, GA 30342
404-851-8523
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