search
Back to results

Denileukine Diftitox for Relapsed ALCL

Primary Purpose

Anaplastic Large-Cell Lymphoma

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Denileukin Diftitox
Denileukin diftitox, ifosfamide, cyclophosphamide, etoposide
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anaplastic Large-Cell Lymphoma focused on measuring lymphoma, pediatric, adolescent, relapsed, refractory, denileukin diftitox, Ontak

Eligibility Criteria

2 Years - 24 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Columbia University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

DD Alone

DD with ICE Chemotherapy

Arm Description

Patients will get Denileukin Diftitox for 5 days every 3 weeks for a total of 4 cycles.

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.

Outcomes

Primary Outcome Measures

Toxicity
Determine response rate
Evaluate safety of combination of Denileukin Diftitox and ICE chemotherapy

Secondary Outcome Measures

Biology Studies of ALCL

Full Information

First Posted
December 3, 2008
Last Updated
May 14, 2013
Sponsor
Columbia University
search

1. Study Identification

Unique Protocol Identification Number
NCT00801918
Brief Title
Denileukine Diftitox for Relapsed ALCL
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2009
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of funding
Study Start Date
December 2008 (undefined)
Primary Completion Date
December 2011 (Anticipated)
Study Completion Date
June 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Columbia University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anaplastic Large-Cell Lymphoma
Keywords
lymphoma, pediatric, adolescent, relapsed, refractory, denileukin diftitox, Ontak

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DD Alone
Arm Type
Other
Arm Description
Patients will get Denileukin Diftitox for 5 days every 3 weeks for a total of 4 cycles.
Arm Title
DD with ICE Chemotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Denileukin Diftitox
Other Intervention Name(s)
Ontak
Intervention Description
Denileukin Diftitox: 18 mcg/kg/day: days 1-5 in cycles 1,2,3,4
Intervention Type
Drug
Intervention Name(s)
Denileukin diftitox, ifosfamide, cyclophosphamide, etoposide
Other Intervention Name(s)
Ontak
Intervention Description
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
Primary Outcome Measure Information:
Title
Toxicity
Time Frame
5 months
Title
Determine response rate
Time Frame
6 months
Title
Evaluate safety of combination of Denileukin Diftitox and ICE chemotherapy
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Biology Studies of ALCL
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
24 Years
Accepts Healthy Volunteers
No
Eligibility 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: 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) 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mitchell S Cairo, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Denileukine Diftitox for Relapsed ALCL

We'll reach out to this number within 24 hrs