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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

Phase 2
2 Years
24 Years
Not Enrolling
Anaplastic Large-Cell Lymphoma

Thank you

Trial Information

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

Despite significant progress in the treatment and outcome for childhood ALCL, the prognosis
for children who develop progressive or recurrent disease is poor with < 30% DFS. Novel
therapies are urgently needed for these subgroups of patients. One potential approach is the
investigation of a new class of receptor targeted cytotoxic fusion proteins (denileukin
diftitox{DD}). We have previously demonstrated that > 85% of children with ALCL express
CD25. The human IL-2 receptor exists in three forms, low (CD25), intermediate (CD122/CD132)
and high (CD25/CD122/CD132) affinity. DD is a recombinant DNA-derived cytotoxic fusion
protein composed of the amino acid sequences for diphtheria toxin fragments followed by the
binding sequences for the interleukin-2 receptor. Malignant cells expressing one or more of
the subunits of the IL-2 receptor are found in certain leukemias and lymphomas including
cutaneous T-cell lymphoma (CTCL). Clinical studies have shown therapeutic efficacy of DD
alone and in combination with CHOP chemotherapy in CD25 expressing malignancies such as
CTCL, CLL and lymphoma. We hypothesize that DD will be safe and efficacious in children with
relapsed ALCL.

Inclusion Criteria:

- Age: Patients must be ≥ 2.00 year and ≤ 24.99 years of age at the time of study

- Diagnosis:

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
performance score.

- 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
starting therapy.

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
case-by-case basis.

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
age, and

- SGPT (ALT) < 3 x upper limit of normal (ULN) for age

- Serum albumin > 2 g/dL.

Exclusion Criteria:

- 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.

Type of Study:


Study Design:

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

Outcome Measure:


Outcome Time Frame:

5 months

Safety Issue:


Principal Investigator

Mitchell S Cairo, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Columbia University


United States: Institutional Review Board

Study ID:




Start Date:

December 2008

Completion Date:

June 2012

Related Keywords:

  • Anaplastic Large-Cell Lymphoma
  • lymphoma
  • pediatric
  • adolescent
  • relapsed
  • refractory
  • denileukin diftitox
  • Ontak
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Anaplastic



Columbia University Medical CenterNew York, New York  10032