Anaplastic Large-Cell LymphomaPhase 2NCT00801918
Denileukine Diftitox for Relapsed ALCL
A Phase 2 study testing Denileukin Diftitox and Denileukin diftitox, ifosfamide, cyclophosphamide, etoposide in people with Anaplastic Large-Cell Lymphoma, run by Columbia University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 24 years
- Conditions the study is for
- Anaplastic Large-Cell Lymphoma
- What is being tested?
- Denileukin Diftitox and Denileukin diftitox, ifosfamide, cyclophosphamide, etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Jun 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 33Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
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
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).
Read the 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.
- Conditions
- Anaplastic Large-Cell Lymphoma
- Being tested
- Denileukin Diftitox, Denileukin diftitox, ifosfamide, cyclophosphamide, etoposide
- Keywords
- lymphoma, pediatric, adolescent, relapsed, refractory, denileukin diftitox, Ontak
- Medical subject headings
- Lymphoma, Large-Cell, Anaplastic, Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Denileukin DiftitoxDrug
Also called Ontak
Denileukin Diftitox: 18 mcg/kg/day: days 1-5 in cycles 1,2,3,4
Denileukin diftitox, ifosfamide, cyclophosphamide, etoposideDrug
Also called Ontak
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
| Study group | Role | What they receive |
|---|---|---|
| DD Alone | Other | Patients will get Denileukin Diftitox for 5 days every 3 weeks for a total of 4 cycles. Receives: Drug: Denileukin Diftitox |
| DD with ICE Chemotherapy | Experimental | 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. Receives: Drug: Denileukin diftitox, ifosfamide, cyclophosphamide, etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity
Measured: 5 months
Determine response rate
Measured: 6 months
Evaluate safety of combination of Denileukin Diftitox and ICE chemotherapy
Measured: 6 months
Secondary outcomes (1)
Biology Studies of ALCL
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2008 (estimated)
- Study startDec 2008
- Primary completionDec 2011 (estimated)
- Study completionJun 2012 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anaplastic Large-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Investigators
- Mitchell S Cairo, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00801918
- Sponsor's protocol ID
- AAAC8963
- Status last verified
- Oct 2009
- First submitted
- 3 Dec 2008
- Last updated
- 15 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00801918
- Acronym / sponsor ID
- AAAC8963
- Conditions
- Anaplastic Large-Cell Lymphoma
- Keywords
- lymphoma, pediatric, adolescent, relapsed, refractory, denileukin diftitox, Ontak
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Dec 2011 (estimated)
- Study completion
- Jun 2012 (estimated)
- First posted
- 4 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DD Alone | Other | Drug: Denileukin DiftitoxPatients will get Denileukin Diftitox for 5 days every 3 weeks for a total of 4 cycles. |
| DD with ICE Chemotherapy | Experimental | Drug: Denileukin diftitox, ifosfamide, cyclophosphamide, etoposideFor 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. |
Who may qualify
- Ages
- 2 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (33 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Denileukin DiftitoxAlso: OntakDenileukin Diftitox: 18 mcg/kg/day: days 1-5 in cycles 1,2,3,4 | Drug | DD Alone |
| Denileukin diftitox, ifosfamide, cyclophosphamide, etoposideAlso: OntakDenileukin 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 | Drug | DD with ICE Chemotherapy |
Primary outcome
Toxicity
Time frame: 5 months
Determine response rate
Time frame: 6 months
Evaluate safety of combination of Denileukin Diftitox and ICE chemotherapy
Time frame: 6 months
1 secondary outcome
Biology Studies of ALCL
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2013.
Related trials for Anaplastic Large-Cell Lymphoma
Not yet recruitingObservational study
BV-CHP Real-life and Biological Evidences in Patients With sALCL
Anaplastic Large Cell Lymphoma
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
RecruitingPhase 1
Azacitidine and Abatacept in Relapsed or Refractory T-Cell Lymphoma
Lymphoma, T Cell, Peripheral, T-cell Lymphoma
Active, not recruitingPhase 1/2
A Study to Assess the Safety, Tolerability, Efficacy, and Drug Levels of BMS-986369 (Golcadomide) in Participants With Relapsed or Refractory T-cell Lymphomas in Japan (GOLSEEK-3)
Relapsed or Refractory T-cell Lymphomas
RecruitingPhase 1
Constitutive IL7R (C7R) Modified Banked Allogeneic CD30.CAR EBVSTS for CD30-Positive Lymphomas
CD30-Positive Diffuse Large B-Cell Lymphoma, Anaplastic Large Cell Lymphoma, T Cell and Null Cell Type
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mitchell S Cairo, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denileukin Diftitox and Denileukin diftitox, ifosfamide, cyclophosphamide, etoposide in people with Anaplastic Large-Cell Lymphoma, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity (time frame: 5 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2013; AzTrials last refreshed its copy on 28 Oct 2026.