Adult T-cell Leukemia-LymphomaPhase 2NCT01626664
KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
A Phase 2 study testing KW-0761, Pralatrexate and gemcitabine plus oxaliplatin in people with Adult T-cell Leukemia-Lymphoma, run by Kyowa Kirin, Inc. at 20 sites in 6 countries.
Trial summary
The purpose of this study is to estimate the overall response rate of subjects with relapsed or refractory Adult T-cell Leukemia-Lymphoma (ATL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult T-cell Leukemia-Lymphoma
- What is being tested?
- KW-0761, Pralatrexate and gemcitabine plus oxaliplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 20 sitesin 6 countries
- Study dates
- Jun 2012to Feb 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and female subjects ≥ 18 years of age
- Confirmed diagnosis of ATL (excluding smoldering subtype)
- Subjects must currently have evidence of disease in at least one of the following:
- Lymph nodes
- Extranodal masses
- Spleen or liver
Show all 13Show fewer
- Skin
- Peripheral blood
- Bone marrow
- Relapsed or refractory after at least one prior systemic therapy regimen for ATL;
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study entry
- Resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE, v.4.0)
- Adequate hematological, hepatic and renal function
Who cannot join
- Smoldering subtype of ATL;
- Lymphomatous or acute subtype subject with > 2 prior systemic therapy regimens and who has not achieved a response (CR or PR) or maintained stable disease for at least 12 weeks on last immediate prior therapy;
- History of allogeneic transplant;
- Autologous hematopoietic stem cell transplant within 90 days of study entry;
- Untreated human immunodeficiency virus (HIV)
- Has known hepatitis C. Patients who are hepatitis C antibody positive but are hepatitis C quantitative PCR negative may be enrolled;
Show all 19Show fewer
- Has hepatitis B based on PCR testing for hepatitis B virus DNA. Patients who are hepatitis B core antibody positive but PCR negative may be enrolled if placed on appropriate anti-hepatitis B virus prophylaxis prior to commencing treatment with KW-0761. Patients who are hepatitis B core antibody positive based on prior vaccination need not receive prophylaxis;
- Have had a malignancy in the past two years except non-melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current PSA < 0.1 µg/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast who is currently without evidence of disease;
- Clinical evidence of central nervous system (CNS) involvement or metastasis. In subjects suspected of having CNS disease, an MRI of the brain and/or lumbar puncture should be done to confirm;
- Psychiatric illness, disability or social situation that would compromise the subject's safety or ability to provide consent, or limit compliance with study requirements;
- Significant uncontrolled intercurrent illness
- Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;
- Known active autoimmune diseases will be excluded (For example; Grave's disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease);
- Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.
- Prior treatment with KW-0761;
- Initiation of treatment with systemic corticosteroids while on study is only permitted for acute and brief complications of underlying disease (e.g., hypercalcemia) or for treatment related side effects (e.g., including pre-medication for infusion reaction, nausea and vomiting). Subjects on systemic corticosteroids prior to enrollment must be off for 7 days before initiation of study treatment, unless specifically indicated for the treatment of hypercalcemia. (subjects may receive inhalation corticosteroids and replacement doses of systemic corticosteroids as needed);
- Initiation of treatment with topical corticosteroids while on study is not permitted except to treat an acute rash. Subjects on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to Pre-treatment Visit may continue use at the same dose, although the investigator should attempt to taper the use to lowest dose tolerable;
- Have had interferon-α and/or zidovudine within 1 week, or anti-neoplastic chemotherapy, radiation, immunotherapy, or investigational medications within 2 weeks of first study treatment;
- Subjects on any immunomodulatory drug. Subjects on any immunomodulatory drug within 4 weeks of their first dose of KW-0761 are also excluded.
Trial locations and contacts
20 sites in 6 countries.
20 sites in 6 countries
United States10 sites
National Cancer Institute
Bethesda, Maryland, 20892
Northwestern University
Chicago, Illinois, 60611
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Miami / Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Memorial Sloan Kettering
New York, New York, 10021
Columbia Presbyterian
New York, New York, 10032
Weill Cornell Medical College
New York, New York, 10065
Washington University School of Medicine
St Louis, Missouri, 63110
Montefiore Medical Center
The Bronx, New York, 10467
United Kingdom3 sites
Guy's Hospital
London, SE1 9RT
Imperial College
London, W2 1PG
Sandwell General Hospital
West Midlands, B71 4HJ
Brazil2 sites
Hospital Universitario Professor Edgard Santos- UFBA
Salvador, Bahia, 40110-060
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Sao Paulo- SP, CEP 05403-000
France2 sites
CHU de Fort de France
Fort de France Cedex, BP 632 97261
Hospital Necker
Paris, 75743
Peru2 sites
Hospital Nacional Edgardo Rebagliati Martins
Lima, Lima11
Instituto Oncologico Miraflores
Lima, Lima18
About this study
Official title: Multi-Center, Open-Label, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
The purpose of this study is to estimate the overall response rate of subjects with relapsed or refractory Adult T-cell Leukemia-Lymphoma (ATL).
Read the detailed description
CCR4 expression in ATL patients has been demonstrated to be very high and has been associated with shorter survival compared with CCR4-negative patients. KW-0761, a monoclonal antibody targeted to CCR4, has been shown to be safe and tolerable in several clinical trials in subjects with a variety of T-cell malignancies, including ATL, mycosis fungoides and Sézary syndrome. The objective of this study is to estimate the overall response rate of KW-0761 for subjects with relapsed or refractory ATL.
- Conditions
- Adult T-cell Leukemia-Lymphoma
- Being tested
- KW-0761, Pralatrexate, gemcitabine plus oxaliplatin, DHAP
- Keywords
- Adult T cell Leukemia-Lymphoma (ATL)
- Medical subject headings
- Leukemia-Lymphoma, Adult T-Cell, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KW-0761Biological
Also called mogamulizumab, POTELIGEO®
1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression
PralatrexateDrug
Also called Folotyn
30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression
gemcitabine plus oxaliplatinDrug
Also called Gemzar, Eloxatin, GemOx
gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression
DHAPDrug
Also called Decadron, Dexasone, Baycadron, Platinol, Depocyt, Ara-C
dexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression
| Study group | Role | What they receive |
|---|---|---|
| KW-0761 | Experimental | anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) Receives: Biological: KW-0761 |
| investigator's choice | Active comparator | Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP Receives: Drug: Pralatrexate; Drug: gemcitabine plus oxaliplatin; Drug: DHAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Overall Response Rate was determined based on the response in all compartments (lymph nodes, extranodal masses, spleen/liver, skin, peripheral blood, and bone marrow), referencing Tsukasaki, 2009 as follows: Complete Response (CR) = All compartments involved with disease must be CR; Uncertified Complete Response (CRu) = > 75% decrease in lymph nodes and/or extranodal disease with all other compartments involved with disease CR; Partial Response (PR) = If any compartment is CR/PR and all other compartments involved with disease are at least SD; Stable Disease (SD) = All compartments involved with disease are SD; Progressive Disease (PD) = PD in any compartment.
Lymph node and extranodal masses response ≥50% decrease by CT, skin response ≥50% decrease in mSWAT score; blood response ≥50% decrease in malignant cells by flow cytometry; normal bone marrow if abnormal at baseline. PD equals New or ≥50% increase in any compartment.
Measured: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first
Secondary outcomes (3)
Progression Free Survival
Progression-free survival was defined as the time from the first date of treatment until the date that PD or death was first reported. Disease progression included PD in any compartment per ATL response criteria, clinical progression at the end of the randomized treatment, or disease progression reported during the follow-up period. The date of PD was the earliest date at which disease progression could be declared.
Measured: From date of randomization until the date of first documented progression, start of alternative therapy, or date of death from any cause, whichever came first, up to 36 months
Overall Survival
The estimates and summary statistics for OS were calculated based on Kaplan-Meier method, and the median OS was 4.9 months for subjects randomized to the mogamulizumab group versus 6.87 months for subjects randomized to the Investigator's Choice group.
Measured: up to 36 months
Change in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score
The FACT-Lym consists of a 27-item general core questionnaire (i.e., Functional Assessment of Cancer Therapy - General [FACT-G]) and a 15-item disease-specific questionnaire (Lymphoma Subscale). The FACT-G includes 4 domains: physical well-being, social/family well-being, emotional well-being, and functional well-being. The total FACT-Lym score (0-168) was obtained by summing individual subscale scores. Higher scores for the scales indicate better quality of life. Change was calculated as the value at the last observation minus the value at baseline.
Measured: From date of randomization until the date of first documented progression, up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2012 (estimated)
- Study startJun 2012
- Primary completionAug 2015
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult T-cell Leukemia-LymphomaStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyowa Kirin, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Kurman, MD, Study director, Kyowa Hakko Kirin Pharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01626664
- Sponsor's protocol ID
- PROTOCOL 0761-009
- Status last verified
- Apr 2024
- First submitted
- 19 Jun 2012
- Last updated
- 25 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Center, Open-Label, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
- ClinicalTrials.gov ID
- NCT01626664
- Acronym / sponsor ID
- PROTOCOL 0761-009
- Conditions
- Adult T-cell Leukemia-Lymphoma
- Keywords
- Adult T cell Leukemia-Lymphoma (ATL)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Kyowa Kirin, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2012
- Primary completion
- Aug 2015 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 25 Jun 2012 (estimated)
- Results
- Posted 15 Jun 2018
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 estimate the overall response rate of subjects with relapsed or refractory Adult T-cell Leukemia-Lymphoma (ATL).
Detailed description
CCR4 expression in ATL patients has been demonstrated to be very high and has been associated with shorter survival compared with CCR4-negative patients. KW-0761, a monoclonal antibody targeted to CCR4, has been shown to be safe and tolerable in several clinical trials in subjects with a variety of T-cell malignancies, including ATL, mycosis fungoides and Sézary syndrome. The objective of this study is to estimate the overall response rate of KW-0761 for subjects with relapsed or refractory ATL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| KW-0761 | Experimental | Biological: KW-0761anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) |
| investigator's choice | Active comparator | Drug: Pralatrexate, Drug: gemcitabine plus oxaliplatin, Drug: DHAPComparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Males and female subjects ≥ 18 years of age
- Confirmed diagnosis of ATL (excluding smoldering subtype)
- Subjects must currently have evidence of disease in at least one of the following:
- Relapsed or refractory after at least one prior systemic therapy regimen for ATL;
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study entry
Key exclusion criteria (19 listed)
- Smoldering subtype of ATL;
- Lymphomatous or acute subtype subject with > 2 prior systemic therapy regimens and who has not achieved a response (CR or PR) or maintained stable disease for at least 12 weeks on last immediate prior therapy;
- History of allogeneic transplant;
- Autologous hematopoietic stem cell transplant within 90 days of study entry;
- Untreated human immunodeficiency virus (HIV)
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 |
|---|---|---|
| KW-0761Also: mogamulizumab, POTELIGEO®1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression | Biological | KW-0761 |
| PralatrexateAlso: Folotyn30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression | Drug | investigator's choice |
| gemcitabine plus oxaliplatinAlso: Gemzar, Eloxatin, GemOxgemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression | Drug | investigator's choice |
| DHAPAlso: Decadron, Dexasone, Baycadron, Platinol, Depocyt, Ara-Cdexamethasone 40 mg on Day 1-4, cisplatin 100 mg/m2 on Day 1 followed by 2 doses of cytarabine 2000 mg/m2 every 4 weeks until progression | Drug | investigator's choice |
Primary outcome
Overall Response Rate
Time frame: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first
Overall Response Rate was determined based on the response in all compartments (lymph nodes, extranodal masses, spleen/liver, skin, peripheral blood, and bone marrow), referencing Tsukasaki, 2009 as follows: Complete Response (CR) = All compartments involved with disease must be CR; Uncertified Complete Response (CRu) = > 75% decrease in lymph nodes and/or extranodal disease with all other compartments involved with disease CR; Partial Response (PR) = If any compartment is CR/PR and all other compartments involved with disease are at least SD; Stable Disease (SD) = All compartments involved with disease are SD; Progressive Disease (PD) = PD in any compartment. Lymph node and extranodal masses response ≥50% decrease by CT, skin response ≥50% decrease in mSWAT score; blood response ≥50% decrease in malignant cells by flow cytometry; normal bone marrow if abnormal at baseline. PD equals New or ≥50% increase in any compartment.
3 secondary outcomes
Progression Free Survival
Time frame: From date of randomization until the date of first documented progression, start of alternative therapy, or date of death from any cause, whichever came first, up to 36 months
Overall Survival
Time frame: up to 36 months
Change in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score
Time frame: From date of randomization until the date of first documented progression, up to 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Michael Kurman, MD study director
Kyowa Hakko Kirin Pharma, Inc.
20 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KW-0761, Pralatrexate and gemcitabine plus oxaliplatin in people with Adult T-cell Leukemia-Lymphoma, run by Kyowa Kirin, Inc. at 20 sites in 6 countries.
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 13 inclusion and 19 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: finished, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, United Kingdom, Brazil, France, Peru and 1 more country. 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?
Yes. Results are posted in the registry (first posted 15 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (time frame: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first). 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 25 Apr 2024.