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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00659425
First received: April 10, 2008
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

To estimate maximum cummulative dose (MTCD) of CAT-8015 that can be safely administered to a patient.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Non-Hodgkin's Lymphoma
Drug: CAT-8015 (Moxetumomab Pasudotox)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • To characterize the tolerability and safety profile. [ Time Frame: 30 days after last dose of study drug/per subject ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 76
Study Start Date: September 2008
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
CAT-8015
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   6 Months to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00659425

Locations
United States, California
Research Site
Los Angeles, California, United States
United States, Maryland
Research Site
Bethesda, Maryland, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, Tennessee
Research Site
Memphis, Tennessee, United States
Canada, Ontario
Research Site
Toronto, Ontario, Canada
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Trishna Goswami, M.D. MedImmune LLC
  More Information

Additional Information:
No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00659425     History of Changes
Other Study ID Numbers: CAT-8015-1004
Study First Received: April 10, 2008
Last Updated: August 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 27, 2014