A Phase II Pilot Multicenter Study of Denileukin Diftitox Alone and in Combination With ICE (ICED) Chemotherapy in Children, Adolescents and Young Adults (CAYA) With Relapsed or Refractory Anaplastic Large Cell Lymphoma
- Age: Patients must be ≥ 2.00 year and ≤ 24.99 years of age at the time of study
Patients must have previous histologic verification of anaplastic large cell lymphoma
(ALCL). Patients must be in first, second or third relapse or initial induction failure.
- Disease Status: Patients must have measurable radiographic disease.
- Performance Level: Karnofsky > 60% for patients > 16 years of age and Lansky > 60 for
patients <16 years of age. Patients who are unable to walk because of paralysis, but who
are up in a wheelchair, will be considered ambulatory for the purpose of assessing the
- Prior Therapy
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study. Patients who are
post-allogeneic transplant should be off immunosuppressive agents prior to starting
therapy. Steroid doses should also be stable or decreasing for at least 1 week prior to
Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this
study (6 weeks if prior nitrosourea).
Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a
biologic agent. For agents that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse events
are known to occur. These patients must be discussed with the Study Chair on a
XRT: > 2 wks for local palliative XRT (small port); > 2 months must have elapsed if prior
TBI, craniospinal XRT or if > 50% radiation of pelvis; > 6 wks must have elapsed if other
substantial BM radiation.
Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and > 2
months must have elapsed since SCT.
Patients may not have received prior therapy with Denileukin Diftitox
- Organ Function Requirements
Adequate Bone Marrow Function Defined As:
1. For patients without bone marrow involvement:
- Peripheral absolute neutrophil count (ANC) > 1,000
- Platelet count > 100,000 (transfusion independent)
- Hemoglobin > 8.0 gm (RBC transfusion independent)
2. For patients with bone marrow involvement:
- Peripheral absolute neutrophil count (ANC) > 1,0
- Platelet count > 20,000 (may receive platelet transfusions)
- Hemoglobin > 8.0 (may receive RBC transfusions)
Adequate Renal Function Defined As:
Creatinine clearance or radioisotope GFR 70mL/min/1.73m2
A serum/plasma creatinine GFR calculation using the Schwartz formula (Schwartz et al. J.
Peds, 106:522, 1985)
Estimated Creatinine Clearance (in mL/min/1.73 m2) = (k)(L)/Pcr
Where L = child's length in cm Pcr = plasma (or serum) creatinine (in mg/dL)
k Values = 0.33 low birth weight infant 0.45 term infant 0.55 child 0.55 adolescent
female 0.70 adolescent male
Adequate Liver Function Defined As:
- Bilirubin (sum of conjugated + unconjugated) < 1.5 x upper limit of normal (ULN) for
- SGPT (ALT) < 3 x upper limit of normal (ULN) for age
- Serum albumin > 2 g/dL.
- Patients must not be currently receiving another investigational drug.
- Patients must not be currently receiving other anti-cancer agents.
- Patients must have a negative pregnancy test and Nursing mothers must agree not to
- Patients who have a documented uncontrolled infection requiring IV antibiotics
- Patients with CNS disease are not eligible.