CAT-8015 in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by MedImmune LLC
Sponsor:
Collaborator:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00659425
First received: April 10, 2008
Last updated: November 21, 2013
Last verified: November 2013

April 10, 2008
November 21, 2013
September 2008
September 2014   (final data collection date for primary 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. [ Time Frame: End of study ] [ Designated as safety issue: No ]
Estimate the maximum tolerated dose (MTD), defined as the highest dose that can be safely administered to a patient, and establish a safe dose, based on the MTD, for subsequent clinical testing. [ Time Frame: End of study ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00659425 on ClinicalTrials.gov Archive Site
To characterize the tolerability and safety profile. [ Time Frame: 30 days after last dose of study drug/per subject ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
CAT-8015 in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
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 maximum cummulative dose (MTCD) of CAT-8015 that can be safely administered to a patient.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Lymphoblastic Leukemia
  • Non-Hodgkin's Lymphoma
Drug: CAT-8015 (Moxetumomab Pasudotox)
The dose level of the initial cohort will be 5 µg/kg. Cohorts will be at doses of 5, 10, 20, 30, 40, 50, 60.... µg/kg until toxicity supervenes. Following the identification of the MTCD, the MTCD cohort will be expanded to 12 subjects. Dose escalation to a new cohort may not occur until authorization by the medical monitor, which will require all patients from the prior cohorts have reached cycle 1 day 21 without dose limiting toxicity (DLT) if eligible for retreatment
Experimental: 1
CAT-8015
Intervention: Drug: CAT-8015 (Moxetumomab Pasudotox)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
52
June 2017
September 2014   (final data collection date for primary outcome measure)

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.

Both
6 Months to 25 Years
No
Contact: Radhika Parikh 301-398-0000 clinicaltrialenquiries@medimmune.com
Contact: Paola Canelos 301-398-0000 clinicaltrialenquiries@medimmune.com
United States,   Canada
 
NCT00659425
CAT-8015-1004
No
MedImmune LLC
MedImmune LLC
National Cancer Institute (NCI)
Study Director: Trishna Goswami, M.D. MedImmune LLC
MedImmune LLC
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP