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A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Children, Adolescents and Young Adults With Refractory CD22+ Acute Lymphoblastic Leukemia (ALL) or Non-Hodgkin's Lymphoma (NHL)


Phase 1
6 Months
25 Years
Open (Enrolling)
Both
Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma

Thank you

Trial Information

A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Children, Adolescents and Young Adults With Refractory CD22+ Acute Lymphoblastic Leukemia (ALL) or Non-Hodgkin's Lymphoma (NHL)


To estimate the maximum tolerated cummulative dose (MTCD), defined as the highest dose and
number of doses that can be safely administered to a patient, and to establish a safe dose,
based on the MTCD, for subsequent clinical testing.


Inclusion Criteria:



- Histologically confirmed diagnosis of acute lymphoblastic leukemia (ALL) or
non-Hodgkin's lymphoma (NHL) including lymphoblastic lymphoma, Burkitt's lymphoma,
and large cell lymphoma;

- Measurable or evaluable disease. Subjects with ALL should have M2 or M3 bone marrow
classification;

- Evidence of CD22-positive malignancy by one of the following criteria:

- ≥ 30% of malignant cells from a disease site CD22+ by fluorescence-activated cell
sorter (FACS) analysis or; ≥ 15 % of malignant cells from a disease site CD22+ by
immunohistochemistry (IHC).

Stage of disease:

- Subjects must have relapsed or refractory disease and have received at least one
standard chemotherapy and one salvage regimen or allogeneic stem cell transplant;

- In the view of the PI and the primary oncologist, there must be no available
alternative curative therapies and subjects must either be ineligible for a
hematopoietic stem cell transplant (HSCT), have refused HSCT, or have disease
activity that prohibits HSCT at that time;

- Relapse after prior autologous or allogeneic HSCT is allowed. In the event of relapse
after prior allogeneic HSCT, the subject must be at least 100 days post-transplant
and have no evidence of ongoing active graft-vs-host disease;

- Recovered from the acute toxic effects of all prior therapy before entry.

Performance status:

- Subjects greater than or equal to 12 years of age: Eastern Cooperative Oncology Group
(ECOG) score of 0, 1, 2, or 3;

- Subjects < 12 years of age: Lansky scale ≥ 50%;

- Subjects who are unable to walk because of paralysis, but who are up in a wheel chair
will be considered ambulatory for the purpose of calculating the performance score.

Subjects with the following CNS status, are eligible only in the absence of neurologic
symptoms suggestive of CNS leukemia, such as cranial nerve palsy:

- CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin
preparation, regardless of the number of WBCs;

- CNS 2, defined as presence of < 5/µL WBCs in CSF and cytospin positive for blasts, or
> 5/µL WBCs but negative by Steinherz/Bleyer algorithm:

- CNS 2a: < 10/µL RBCs; < 5/µL WBCs and cytospin positive for blasts;

- CNS 2b: ≥ 10/µL RBCs; < 5/µL WBCs and cytospin positive for blasts;

- CNS 2c: ≥ 10/µL RBCs; ≥ 5/µL WBCs and cytospin positive for blasts but negative by
Steinherz/Bleyer algorithm.

Ability to give informed consent according to applicable regulatory or state requirements.
In the United States: For subjects < 18 years old their legal guardian must give informed
consent. Pediatric subjects will be included in age appropriate discussion and verbal
assent will be obtained for those ≥ 7 years of age;

Must be between the ages of greater than or equal to 6 months and < 25 years;

Female and male subjects with childbearing potential and their sexual partners must agree
to use an approved method of contraception during the study.

Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for participation in the
study:

- Isolated testicular or Central Nervous System (CNS) ALL;

Hepatic function:

- Inadequate liver function defined as total bilirubin > 2 × upper limit of normal
(ULN) (except in the case of subjects with documented Gilbert's disease > 5 × ULN) or
transaminases (ALT and aspartate aminotransferase [AST]) > 5 × ULN based on age- and
laboratory-specific normal ranges;

Renal function:

With greater than age-adjusted normal serum creatinine (see Table below) and a creatinine
clearance > 60 mL/min/1.73 m2.

Age(Years)- Maximum Serum Creatinine (mg/dl)[≤5,0.8] [5 < age less than or equal to
10,1.0] [10 < age less than or equal to 15,1.2 [> 15, 1.5]

Hematologic function:

- For non-leukemic subjects only, the absolute neutrophil count (ANC) < 1000/cmm, or
platelet count < 50,000/cmm, if these cytopenias are not judged by the investigator
to be due to underlying disease (ie potentially reversible with anti-neoplastic
therapy);

- A subject will not be excluded because of pancytopenia ≥ Grade 3 if it is due to
disease, based on the results of bone marrow studies;

Subjects with CNS 3 disease (presence of ≥ 5/µL WBCs in CSF and cytospin positive for
blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS
leukemia);

Radiologically-detected CNS lymphoma;

Laboratory findings consistent with Grade ≥ 3 disseminated intravascular coagulation (DIC)
or any Grade 2 DIC that does not correct;

Hyperleukocytosis (≥ 50,000 blasts/µL) or rapidly PD that in the estimation of the
investigator and sponsor would compromise ability to complete study therapy;

Pregnant or breast-feeding females;

Prior treatment with CAT-3888 (BL22) or any pseudomonas-exotoxin-containing compound;

Recent prior therapy:

Systemic chemotherapy ≤ 2 weeks (6 weeks for nitrosoureas) and radiation therapy ≤ 3 weeks
prior to starting study drug;

Exceptions:

1. There is no time restriction in regard to prior intrathecal chemotherapy provided
there is complete recovery from any acute toxic effects of such;

2. Subjects receiving corticosteroids or hydroxyurea are allowed provided there has been
no increase in dose for at least 2 weeks prior to starting study drug;

3. For radiation therapy: the volume of bone marrow treated is less than 10% and also
the subject has measurable disease outside the radiation port;

4. Subjects who relapse while receiving standard ALL maintenance chemotherapy will not
be required to have a washout period before entry into this study.

Other investigational agents currently or within 30 days prior to entry;

Less than or equal to 1 month prior monoclonal antibody therapy (eg, rituximab).

Subjects with contraindication to corticosteroid administration;

HIV positive serology (due to increased risk of severe infection and unknown interaction
of CAT-8015 with antiretroviral drugs);

Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B
surface antigen [HBsAg]) or hepatitis C and elevated liver transaminases(defined as above
the ULN per the institution normal ranges);

Uncontrolled, symptomatic, intercurrent illness including but not limited to infection,
congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric
illness, malaria infection, or social situations that would limit compliance with study
requirements;

Second malignancy other than non-basal cell carcinoma of the skin or in situ carcinoma of
the cervix, unless the tumor was treated with curative intent at least two years
previously and subject is in remission.

Any physical, social, or psychiatric condition which in the opinion of the investigator
would prevent effective cooperation or participation in the study.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Estimate the maximum tolerated cummulative dose (MTCD), defined as the highest dose and number of doses that can be safely administered to a patient, and establish a safe dose, based on the MTCD, for subsequent clinical testing.

Outcome Time Frame:

End of study

Safety Issue:

No

Principal Investigator

Ramy Ibrahim, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

MedImmune LLC

Authority:

United States: Food and Drug Administration

Study ID:

CAT-8015-1004

NCT ID:

NCT00659425

Start Date:

September 2008

Completion Date:

November 2016

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Non-Hodgkin's Lymphoma
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin

Name

Location

Research SiteBaltimore, Maryland  
Research SiteBeverly, Massachusetts  
Research SiteChattanooga, Tennessee