Denileukine Diftitox for Relapsed ALCL

• Status: Withdrawn
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine is Denileukin diftitox will be safe, well tolerated and induce a significant overall response alone and in combination with chemotherapy: ifosfamide, carboplatin and etoposide (ICE) and will be safe and well tolerated in a population of children, adolescents and young adults with relapsed or refractory anaplastic large cell lymphoma (ALCL).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Treatments: Cyclophosphamide; Denileukin diftitox; Etoposide; Etoposide phosphate; Ifosfamide; Interleukin-2; Isophosphamide mustard

Criteria

Inclusion Criteria:

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

• 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

OR

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 breast-feed.

• Patients who have a documented uncontrolled infection requiring IV antibiotics

• Patients with CNS disease are not eligible.