Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Novel Combination Therapy in the Treatment of Relapsed and Refractory Aggressive B-Cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02436707
Recruitment Status : Recruiting
First Posted : May 7, 2015
Last Update Posted : March 13, 2019
Sponsor:
Collaborators:
Janssen, LP
Roche Pharma AG
Information provided by (Responsible Party):
Canadian Cancer Trials Group

Brief Summary:
The purpose of this study is to find out what effects new combinations of treatment will have this disease. In this clinical trial, the study treatment options currently are ibrutinib plus R-GDP, or R-GDP alone.

Condition or disease Intervention/treatment Phase
Lymphoma Drug: Ibrutinib Drug: Rituximab Drug: Gemcitabine Drug: Dexamethasone Drug: Cisplatin Drug: Mesna Drug: Cyclophosphamide Drug: Etoposide Drug: G-CSF Phase 2

Detailed Description:

R-GDP has been used to treat many people with lymphoma. Ibrutinib has been shown to benefit people with certain types of lymphoma. They have not previously been given together.

This research is being done to try to find new combinations of treatment that may be better for treating patients with this disease. It is not clear however if these treatments can offer better results than standard treatment.

The standard or usual treatment of this disease is treatment with rituximab plus gemcitabine, dexamethasone, and cisplatin (R-GDP).


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 320 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Stage Randomized Phase II Study of Novel Combination Therapy in the Treatment of Relapsed and Refractory Aggressive B-Cell Lymphoma
Actual Study Start Date : May 5, 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Active Comparator: R-GDP

Rituximab - 375 mg/m2 IV, 1.5 - 6 hours D1 (prior to cisplatin);

Gemcitabine - 1000 mg/m2, IV 30 min D1, D8;

Dexamethasone - 40 mg daily PO D1 - D4;

Cisplatin - 75 mg/m2 IV, 1 hour D1;

Drug: Rituximab
Drug: Gemcitabine
Drug: Dexamethasone
Drug: Cisplatin
Experimental: Ibrutinib plus R-GDP (ACCRUAL COMPLETE)

Ibrutinib 560 mg PO -- D1 - D21

Rituximab 375 mg/m2 IV 1.5 - 6 hours D1 (prior to cisplatin)

Gemcitabine 1000 mg/m2 IV 30 min D1, D8

Dexamethasone 40 mg daily PO -- D1 - D4

Cisplatin 75 mg/m2 IV 1 hour D1

Drug: Ibrutinib
Drug: Rituximab
Drug: Gemcitabine
Drug: Dexamethasone
Drug: Cisplatin
Experimental: R-DICEP

Rituximab 375 mg/m2 IV 1.5-6hrs Day 1 and Day 5 prior to Cisplatin

Mesna 1.75 g/m2 IV 24 hour Cycle 1, Day 2, Day 3 and Day 4

Cyclophosphamide, 1.75 g/m2 IV 2 hours, Day 2, Day 3 and Day 4

Etoposide 350 mg/m2 IV 2 hours, Day 2, Day 3 and Day 4

Cisplatin 35 mg/m2 IV, 2 hours, Day 2, Day 3 and Day 4

G-CSF 300 mcg (<60kg); 480 mcg (60-90kg); 600 mcg (>90kg); SC, Daily, starting Day 15 until apheresis completed.

Drug: Rituximab
Drug: Cisplatin
Drug: Mesna
Drug: Cyclophosphamide
Drug: Etoposide
Drug: G-CSF



Primary Outcome Measures :
  1. Measure overall response rate [ Time Frame: 2 years ]
    To determine the overall response rate (complete and partial response) to novel combination therapy in patients with relapsed and refractory aggressive B cell lymphoma


Secondary Outcome Measures :
  1. Number and severity of adverse events [ Time Frame: 2 years ]
    To evaluate the tolerability and toxicity of novel combinations. Adverse events will be monitored on an ongoing basis by the central office and their frequencies reported annually at investigators' meetings. Safety and tolerability will be reviewed in the first six patients assigned to ibrutinib plus R-GDP as part of a safety run-in. Ibrutinib dose will be reduced for subjects subsequently enrolled if necessary

  2. Transplantation rate [ Time Frame: 2 years ]
    A non-inferiority analysis of transplantation rate will be conducted with 10% non-inferiority margin. The one-sided 80% asymptotic confidence limit of the difference in transplantation rate will be calculated between treatment and control arms.

  3. Stem cell collection rate [ Time Frame: 2 years ]
    Stem cell collection rate defined as collection of ≥ 2 x 106 CD34+ cells/kg.

  4. Event free Survival Rate [ Time Frame: 2 years ]
    • Event free survival (EFS) at one year defined as time from study entry to any treatment failure including disease progression, or discontinuation of treatment for any reason

  5. Overall Survival [ Time Frame: 2 years ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologic diagnosis for one of the following histologies according to the World Health Organization: documented at initial diagnosis or at relapse:

    • Diffuse large cell lymphoma, B-cell (includes primary mediastinal B-cell lymphoma, T-cell rich B-cell lymphoma);
    • Previous indolent lymphoma (follicular lymphoma, marginal zone lymphoma, including extranodal MALT lymphoma, lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at most recent relapse (biopsy proof of transformation is mandatory);
    • Unclassifiable B-cell lymphoma with indeterminate features between diffuse large B-cell lymphoma and Burkitt lymphoma.
  • Biopsy proof of disease at initial diagnosis is mandatory. A biopsy at relapse is preferred but not mandatory. Participating centres must designate a local reference expert pathologist who will confirm the diagnosis for the patients enrolled at that centre.
  • Patients must be CD20+ in order to be eligible for the study.
  • Clinically and/or radiologically measurable disease (one site bidimensionally measurable). Measurements/ evaluations must be done within 28 days prior to randomization.
  • Prior FDG-PET scan, if done at baseline, must be positive (known FDG-avid lymphoma)
  • Patients with de novo aggressive B-cell lymphoma must have relapsed or progressed, or have biopsy proven refractory disease, after 1 prior line of therapy (R-CHOP chemotherapy or equivalent). Patients with histological transformation from low grade lymphoma may have had up to 3 prior treatment regimens. Patients with transformed low grade lymphoma treated with a non-anthracycline regimen may be enrolled at investigator discretion.
  • Patient age is ≥16 years. Patients older than 65 years of age are not recommended for this study.
  • ECOG performance status of 0, 1, 2 or 3.
  • Patient must be considered fit for intensive chemotherapy and ASCT, and an appropriate candidate to receive second-line salvage chemotherapy and ASCT.
  • Life expectancy > 90 days.
  • Laboratory Requirements: (must be done within 14 days of randomization)

Hematology:

  • Granulocytes (AGC) ≥ 1.0 x 10^9/L (independent of growth factor support)
  • Platelets ≥ 100 x 10^9/L (50 x 10^9/L if bone marrow involvement by lymphoma, independent of transfusion support)

Biochemistry:

  • AST and ALT ≤ 3x ULN
  • Serum total bilirubin ≤ 1.5x ULN (≤ 5x ULN if Gilberts Disease)
  • Serum Creatinine ≤ 1.5x ULN (or estimated GFR of ≥ 40 mL/min/1.73m2 using Cockcroft Gault formula).

Women must be post-menopausal, surgically sterile or use reliable forms of contraception while on study. Women of child bearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. These restrictions apply for 12 months (1 year) after the last dose of study drug.

  • Women of childbearing potential must have a pregnancy test taken (either by serum beta-human chorionic gonadotropin [B-hCG]) or urine) and proven negative within 14 days prior to randomization. Women who are pregnant or breastfeeding are ineligible for this study.

Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.

Patients must be accessible for treatment and follow up. Patients randomized on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.

In accordance with CCTG policy, protocol treatment is to begin within 5 working days of patient randomization.

Exclusion Criteria:

  • Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer and superficial bladder cancer, curatively treated in-situ cancer of the cervix or breast, or localized excised prostate cancer, other solid tumours curatively treated with no evidence of disease for ≥ 3 years.
  • Active and uncontrolled central nervous system involvement, meningeal or parenchymal. Patients with CNS disease at initial presentation and who are in a CNS CR at the time of relapse are eligible. MRI scanning and / or lumbar puncture should be performed if there is clinical suspicion of active CNS disease.
  • Major surgery performed within 10 days of randomization.
  • Known history of human immunodeficiency virus (HIV), active Hepatitis C Virus infection, active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Patients with Hepatitis B serology suggestive of infection are eligible if they are HBV DNA negative and concurrently treated with anti-viral therapy. Patients with a past history of hepatitis C who have eradicated the virus are eligible.
  • Patients who have been vaccinated with live, attenuated vaccines within 4 weeks of randomization.
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
  • Any serious active disease or co-morbid medical condition, including psychiatric illness, judged by the local investigator to preclude safe administration of the planned protocol treatment or required follow-up.
  • Any other serious intercurrent illness, life threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or preclude safe administration of the planned protocol treatment or required follow-up, including (for example):

    • active, uncontrolled bacterial, fungal, or viral infection;
    • clinically significant cardiac dysfunction or cardiovascular disease.
  • Pregnant or lactating females, or women of childbearing potential not willing to use an adequate method of birth control for the duration of the study.
  • Patients are not eligible if they have a known hypersensitivity to the study drugs or their components.

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): NCT02436707


Contacts
Layout table for location contacts
Contact: Annette Hay 613-533-6430 ahay@ctg.queensu.ca

Locations
Layout table for location information
Canada, Alberta
Tom Baker Cancer Centre Recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Douglas A. Stewart    403 521-3347      
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Neil Sun Chua    780 432-8340      
Canada, British Columbia
BCCA - Vancouver Cancer Centre Suspended
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Manitoba
CancerCare Manitoba Suspended
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
The Moncton Hospital Recruiting
Moncton, New Brunswick, Canada, E1C 6Z8
Contact: Nizar Abdel-Samad    506 870-2404      
The Vitalite Health Network - Dr. Leon Richard Suspended
Moncton, New Brunswick, Canada, E1C 8X3
Canada, Nova Scotia
QEII Health Sciences Centre Recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Contact: Mary-Margaret Keating    902 473-7006      
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Graeme Fraser    905 575-7820      
Kingston Health Sciences Centre Recruiting
Kingston, Ontario, Canada, K7L 2V7
Contact: Jill Dudebout    613 533-2946      
Ottawa Hospital Research Institute Suspended
Ottawa, Ontario, Canada, K1H 8L6
Odette Cancer Centre Suspended
Toronto, Ontario, Canada, M4N 3M5
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: John Kuruvilla    416 946-2827      
Canada, Quebec
CIUSSS de l'Est-de-I'lle-de-Montreal Suspended
Montreal, Quebec, Canada, H1T 2M4
CHUM-Centre Hospitalier de l'Universite de Montreal Suspended
Montreal, Quebec, Canada, H2X 3E4
CHU de Quebec-Hopital l'Enfant-Jesus (HEJ) Recruiting
Quebec City, Quebec, Canada, G1J 1Z4
Contact: Jean-Francois Larouche    418 649-5726      
Canada, Saskatchewan
Allan Blair Cancer Centre Suspended
Regina, Saskatchewan, Canada, S4T 7T1
Sponsors and Collaborators
Canadian Cancer Trials Group
Janssen, LP
Roche Pharma AG
Investigators
Layout table for investigator information
Study Chair: Michael Crump Univ. Health Network-OCI/Princess Margaret Hospital, Toronto ON Canada
Study Chair: John Kuruvilla Univ. Health Network-Princess Margaret Hospital, Toronto ON Canada

Layout table for additonal information
Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT02436707     History of Changes
Other Study ID Numbers: LY17
First Posted: May 7, 2015    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cisplatin
Dexamethasone
Gemcitabine
Cyclophosphamide
Rituximab
Etoposide
Etoposide phosphate
Dexamethasone acetate
BB 1101
Antineoplastic Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Protease Inhibitors