Denileukine Diftitox for Relapsed ALCL

This study has been withdrawn prior to enrollment.
(Lack of funding)
Sponsor:
Information provided by:
Columbia University
ClinicalTrials.gov Identifier:
NCT00801918
First received: December 3, 2008
Last updated: May 14, 2013
Last verified: October 2009
  Purpose

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).


Condition Intervention Phase
Anaplastic Large-Cell Lymphoma
Drug: Denileukin Diftitox
Drug: Denileukin diftitox, ifosfamide, cyclophosphamide, etoposide
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Toxicity [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Determine response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Evaluate safety of combination of Denileukin Diftitox and ICE chemotherapy [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Biology Studies of ALCL [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: December 2008
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
DD Alone
Patients will get Denileukin Diftitox for 5 days every 3 weeks for a total of 4 cycles.
Drug: Denileukin Diftitox
Denileukin Diftitox: 18 mcg/kg/day: days 1-5 in cycles 1,2,3,4
Other Name: Ontak
Experimental: DD with ICE Chemotherapy
For patients who show a response to DD alone after 4 cycles or for patients who show progressive disease after 2 cycles, DD will be given with ICE chemotherapy for 2 cycles.
Drug: Denileukin diftitox, ifosfamide, cyclophosphamide, etoposide
Denileukin Diftitox: 18 mcg/kg/day days 1-2 in cycles 5 and 6 Ifosfamide: 3000mg/m²/IV/d X 3 days + Mesna 3000 mg/m2/d X 3 days Carboplatin: 635mg/m2/d X 1 day Etoposide: 100mg/m2/d X 3 days
Other Name: Ontak

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years to 24 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00801918

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Mitchell S Cairo, MD Columbia University
  More Information

No publications provided

Responsible Party: Mitchell Cairo, MD, Prinicpal Investigator, Columbia University Medical Center
ClinicalTrials.gov Identifier: NCT00801918     History of Changes
Other Study ID Numbers: AAAC8963
Study First Received: December 3, 2008
Last Updated: May 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
lymphoma
pediatric
adolescent
relapsed
refractory
denileukin diftitox
Ontak

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell
Cyclophosphamide
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Denileukin diftitox
Etoposide
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on July 29, 2014