Clinical trial NCT00313053: Study of mAb 216 With Chemotherapy for Treatment of Pediatric Relapsed or Refractory B-progenitor Acute Lymphoblastic Leukemia
Official title: A Phase I Study of mAb 216 With Chemotherapy for the Treatment of Pediatric Patients With Relapsed or Refractory B-progenitor Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Leukemia, Lymphocytic, Acute
Leukemia
Acute Lymphoid Leukemia (ALL)
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2006-04-11
Enrollment: 4
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase I trial in patients with relapsed or refractory leukemia of a human monoclonal antibody that kills B cell acute lymphoblastic leukemia. The trial will study the safety, pharmacokinetics, and anti-tumor activity of the antibody given as a single agent and with vincristine.


Eligibility criteria: Inclusion Criteria:- Patients must be \> than 12 months at the time of study entry.

* Patients must have had histologic verification of B-lineage ALL with bone marrow relapse or refractory disease that is unresponsive to traditional chemotherapy.
* For patients WITHOUT prior allogeneic bone marrow transplant (BMT):

  * Second or subsequent bone marrow relapse
  * Primary refractory marrow disease
  * M3 marrow (\> 25% blasts)
* For patients WITH prior allogeneic BMT:

  * First or subsequent bone marrow relapse post-BMT
  * M3 marrow or M2 (\> 5% and \< 25% blasts) if cytogenetic or variable number tandem repeat (VNTR) confirmation
* Confirmation of antibody reactivity
* Patient's leukemic blasts (peripheral blood or marrow) must be documented to bind mAb 216 in vitro (Teng lab).
* Patient's red blood cell (RBC) documented to NOT express fetal "i" antigen and RBC shown to NOT bind mAb 216 in vitro (Teng lab)
* Patient must not be eligible for therapies of higher priority
* Performance level Karnofsky 50% for patients \> 10 years of age and Lansky \>= 50 for patients \<= 10 years of age.
* Life expectancy must be at least 8 weeks.
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study:

  * Myelosuppressive chemotherapy: must not have been received within 2 weeks of entry onto this study.
  * Biologic: at least 7 days since the completion of therapy with a biologic agent.
* No hematologic criteria for white blood cell (WBC), hemoglobin (Hgb), or platelets
* Patients with thrombocytopenia should be responsive to platelet transfusions and must not have uncontrolled bleeding.
* Adequate renal function defined as: a serum creatinine that is less than or equal to 1.5 x normal for age
* Adequate liver function defined as: total bilirubin \<= 1.5 x upper limit of normal (ULN) for age, and SGPT (ALT) \<= 5 x upper limit of normal (ULN) for age
* Adequate cardiac function defined as: shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by gated radionuclide study.
* All patients and/or their parents or legal guardians must sign a written informed consent/assent.
* All Institutional Review Board (IRB) and Food and Drug Administration (FDA) requirements for human studies must be met. Exclusion Criteria:- Central nervous system (CNS) 3 or refractory CNS leukemia
* Isolated extramedullary relapse
* Uncontrolled infection
* Lack of mAb 216 binding to patient's leukemic blasts in vitro
* Binding of mAb 216 to the"i" antigen on patient's erythrocytes
* Prior treatment with rituximab

Primary outcomes:
measure: Maximum tolerable dose without toxicity
measure: Safety
Secondary outcomes:
measure: Decrease in leukemic blasts
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Clare J. Twist M.D.
role: PRINCIPAL_INVESTIGATOR
References: