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

PRIMARY OBJECTIVES:

I. Evaluate the safety and determine the maximum tolerated dose (MTD) of 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 ADCT-602 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 ADCT-602 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.

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)