KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
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| ClinicalTrials.gov Identifier: NCT01626664 |
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Recruitment Status :
Completed
First Posted : June 25, 2012
Results First Posted : June 15, 2018
Last Update Posted : September 19, 2018
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Sponsor:
Kyowa Kirin Pharmaceutical Development, Inc.
Information provided by (Responsible Party):
Kyowa Kirin Pharmaceutical Development, Inc.
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Brief 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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Adult T-cell Leukemia-Lymphoma | Biological: KW-0761 Drug: Pralatrexate Drug: gemcitabine plus oxaliplatin Drug: DHAP | Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 71 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Study Start Date : | June 2012 |
| Actual Primary Completion Date : | August 2015 |
| Actual Study Completion Date : | February 2018 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: KW-0761
anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab)
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Biological: KW-0761
1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression
Other Names:
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Active Comparator: investigator's choice
Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP
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Drug: Pralatrexate
30 mg/m2 weekly for 3 weeks followed by 1 week of no therapy until progression
Other Name: Folotyn Drug: gemcitabine plus oxaliplatin gemcitabine 1000 mg/m2, followed by oxaliplatin 100 mg/m2 every 2 weeks until progression
Other Names:
Drug: DHAP 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
Other Names:
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Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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 ]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.
- Overall Survival [ Time Frame: up to 36 months ]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.
- 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 ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Males and female subjects ≥ 18 years of age
- Confirmed diagnosis of ATL (excluding smoldering subtype)
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Subjects must currently have evidence of disease in at least one of the following:
- Lymph nodes
- Extranodal masses
- Spleen or liver
- 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
Exclusion Criteria:
- 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;
- 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01626664
Locations
Show 20 study locations
Sponsors and Collaborators
Kyowa Kirin Pharmaceutical Development, Inc.
Investigators
| Study Director: | Michael Kurman, MD | Kyowa Hakko Kirin Pharma, Inc. |
| Responsible Party: | Kyowa Kirin Pharmaceutical Development, Inc. |
| ClinicalTrials.gov Identifier: | NCT01626664 |
| Other Study ID Numbers: |
PROTOCOL 0761-009 |
| First Posted: | June 25, 2012 Key Record Dates |
| Results First Posted: | June 15, 2018 |
| Last Update Posted: | September 19, 2018 |
| Last Verified: | March 2018 |
Keywords provided by Kyowa Kirin Pharmaceutical Development, Inc.:
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Adult T cell Leukemia-Lymphoma (ATL) |
Additional relevant MeSH terms:
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Lymphoma Leukemia Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, Lymphoid Gemcitabine |
Oxaliplatin Mogamulizumab Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |