A Phase IB Study Of The BTKi CC-292 Combined With Lenalidomide In Adults Patients With Relapsed/Refractory B-Cell Lymphoma (CLEAR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by The Lymphoma Academic Research Organisation
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:
NCT01766583
First received: October 29, 2012
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

This is an open label, 3 + 3 dose escalation study, to determine the MTD, safety, efficacy and PK profiles for subjects with relapsed/refractory B-cell malignancies when using CC-292 and lenalidomide combination therapy. Subjects will be followed for disease progression and collection of second primary malignancy (SPM) events. This dose escalation will be followed by an exploratory expansion phase in 3 cohorts of 12 patients each.


Condition Intervention Phase
Relapsed/Refractory B-cell Lymphoma
Drug: CC-292 + lenalidomide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE IB STUDY OF THE BTKi CC-292 COMBINED WITH LENALIDOMIDE IN ADULTS PATIENTS WITH RELAPSED/REFRACTORY B-CELL LYMPHOMA

Resource links provided by NLM:


Further study details as provided by The Lymphoma Academic Research Organisation:

Primary Outcome Measures:
  • Determination of the recommended dose of CC-292 and lenalidomide in patients with relapsed/refractory B-cell lymphoma [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    The optimal CC-292 and lenalidomide combination will be determined based on the maximum tolerated dose (MTD), the dose limiting toxicities (DLT) and/or the analysis of adverse events, serious adverse events and toxicities observed during the study


Secondary Outcome Measures:
  • preliminary efficacy signals of the CC-292 + Lenalidomide combination [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Overall response rate and overall response rate, complete and partial response rates, progression free survival, response duration, time to next treatment and overall survival

  • Observed maximum plasma concentration [ Time Frame: 0, 0.5, 1, 2, 4, 6, 8 hours post dose ] [ Designated as safety issue: No ]
  • time to reach maximum observed plasma concentration (Tmax) [ Time Frame: 0, 0.5, 1, 2, 4, 6, 8 hours post dose ] [ Designated as safety issue: No ]
  • Terminal phase rate constant (λz) [ Time Frame: 0, 0.5, 1, 2, 4, 6, 8 hours post dose ] [ Designated as safety issue: No ]
  • plasma decay half-life (t1/2) [ Time Frame: 0, 0.5, 1, 2, 4, 6, 8 hours post dose ] [ Designated as safety issue: No ]
  • Area under the curve from time zero to the last quantifiable concentration [AUC(0-t)] [ Time Frame: 0, 0.5, 1, 2, 4, 6, 8 hours post dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration versus time curve from time zero (predose) to time of the last quantifiable concentration (0-t)

  • Area under the curve from time zero to extrapolated infinity [AUC(0-∞)] [ Time Frame: 0, 0.5, 1, 2, 4, 6, 8 hours post dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration versus time curve (AUC) from time zero (predose)to extrapolated infinity(0-∞)

  • BTk receptor occupancy [ Time Frame: 0 (predose) and 21 days post dose ] [ Designated as safety issue: No ]
    BTK receptor occupancy will be determined in the peripheral blood cells and tumor tissue


Estimated Enrollment: 60
Study Start Date: February 2013
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide and CC-292
Combination of lenalidomide and CC-292.
Drug: CC-292 + lenalidomide
CC-292 + lenalidomide

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histology:

    1. Patients with any type of B-cell Lymphoma except CLL, SLL and Waldenström disease will be eligible during the dose escalation phase
    2. During the expansion phases, patients with DLBCL for cohort A, mantle cell lymphoma for cohort B and any other type of B-cell lymphoma except CLL, SLL and Waldenström disease for cohort C.
  • Other criteria:

    • Signed inform consent
    • Patients should be relapsed or refractory NHL after ≥1 prior Rituximab-containing regimen for which no other type of therapy is of higher priority
    • Aged 18 years or more.
    • ECOG performance status 0-2.
    • Measurable disease defined by at least one single node or tumor lesion > 1.5 cm.
    • Life expectancy of ≥ 90 days (3 months).
    • Patients must be eligible and willing to undergo excisional biopsies of tumor sites with a lymph node of minimum 1 cm at baseline and after 21 days of treatment
    • Females of childbearing potential (FCBP)† must have two negative serum or urine pregnancy tests with a sensitivity of at least 25 mIU/mL before starting lenalidomide - the first test must be performed within 10-14 days before starting lenalidomide treatment and the second test must be performed within 24 hours before starting lenalidomide
    • FCBP must either commit to continued abstinence from heterosexual intercourse or begin two methods of birth control, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to monthly pregnancy testing and must be counseled at a minimum of every 4 weeks about pregnancy precautions and risks of fetal exposure.
    • Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential. Men must also be counseled at a minimum of every 4 weeks about pregnancy precautions and risks of fetal exposure.

Exclusion Criteria:

Previous treatment with lenalidomide or a BTK inhibitor. Central nervous system or meningeal involvement. Contraindication to any drug contained in this regimen Concomitant use of medicines known to cause QT prolongation or torsades de pointes HIV disease, active hepatitis B or C. Any serious active disease or co-morbid medical condition (according to investigator's decision);

Any of the following laboratory abnormalities :

  • Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L).
  • Platelet count < 80,000/mm3 (80 x 109/L)
  • Serum SGOT/AST or SGPT/ALT >3.0 x upper limit of normal (ULN).
  • Serum total bilirubin > 1.5 ULN except in case of hemolytic anemia and Gilbert's syndrome.

Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 50 mL /min Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast or Incidental histological finding of prostate cancer [TNM stage of T1a or T1b]) unless the subject has been free of the disease for ≥ 5 years Any serious medical condition, laboratory abnormality, or psychiatric illnessthat would prevent the subject from signing the informed consent form.

Pregnant or lactating females. Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide and/or pomalidomide.

Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide and/or pomalidomide.

Subjects with ≥ Grade 2 neuropathy. Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy.

Chronic use of proton pump inhibitors, H2 antagonists or antacids or their use in the last 7 days prior to the first CC-292 dose. Patients with chronic gastroesophageal reflux disease, dyspepsia, and peptic ulcer disease, should be carefully evaluated for their suitability for this treatment prior to enrollment in this study. These medications should be avoided throughout the study.

Patients taking corticosteroids during the 4 weeks prior to inclusion, unless administered at a dose equivalent of ≤ 10 mg/day prednisone (over these 4 weeks).

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01766583

Contacts
Contact: Elise HUTASSE +33472669333 elise.hutasse@lysarc.org
Contact: Yvain Robreau +33472669333 yvain.robreau@lysarc.org

Locations
France
Hopital henri mondor Recruiting
Créteil, France, 94010
Contact: Corinne Haioun, PhD    +331 49 81 41 54    corinne.haioun@hmn.aphp.fr   
Principal Investigator: Corinne Haioun, PhD         
Sub-Investigator: Karim Belhadj, MD         
Sub-Investigator: Jehan Dupuis, MD         
Sub-Investigator: Isabelle Gaillard, MD         
CHU de Lille Recruiting
Lille, France, 59037
Contact: Franck Morschhauser, MD    +333 20 44 57 13    franck.morschhauser@chru-lille.fr   
Principal Investigator: Franck Morschhauser, MD         
Sub-Investigator: Louis Terriou, MD         
Sub-Investigator: Sabine Tricot, MD         
Institut Paoli Calmette Recruiting
Marseille, France, 13273
Contact: Réda Bouabdallah, MD    +334 91 22 33 33    BOUABDALLAHR@ipc.unicancer.fr   
Principal Investigator: Réda Bouabdallah, MD         
Sub-Investigator: Florence Broussais-Guillaumot, MD         
Sub-Investigator: Diane Coso, MD         
Sub-Investigator: Jean-Marc SCHIANO DE COLELLA, MD         
CHU de Nantes Recruiting
Nantes, France, 44093
Contact: Steven Le Gouill, PhD    +332 40 08 32 71      
Principal Investigator: Steven Le Gouill, PhD         
Sub-Investigator: Thomas Gastinne, MD         
Sub-Investigator: Nicolas Blin, MD         
Sub-Investigator: Cyrille Touzeau, MD         
Sub-Investigator: Viviane DUBRUILLE, MD         
Sub-Investigator: Béatrice Mahe, MD         
Sub-Investigator: Virginie ROLLAND, MD         
Sub-Investigator: Aline CLAVERT, MD         
CHU Lyon Sud Recruiting
Pierre Bénite, France, 69495
Contact: Gilles Salles, PhD    +334 78 86 43 01    gilles.salles@chu-lyon.fr   
Principal Investigator: Gilles Salles, PhD         
Sub-Investigator: Bertrand Coiffier, PhD         
Sub-Investigator: Fadhela Bouafia, MD         
Sub-Investigator: Daniel Espinouse, MD         
Sub-Investigator: Lionel Karlin, MD         
Sub-Investigator: Laure Lebras, MD         
Sub-Investigator: Anne-Sophie Michallet, MD         
Sub-Investigator: Catherine Traulle, MD         
CHU de Toulouse Recruiting
Toulouse, France, 31059
Contact: Loïc Ysebaert, MD    +335 61 77 20 78    ysebaert.l@chu-toulouse.fr   
Principal Investigator: Loïc Ysebaert, MD         
Sub-Investigator: Lucie Oberic, MD         
Sub-Investigator: Murielle Roussel, MD         
Sub-Investigator: Benjamin Hebraud, MD         
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Celgene Corporation
Investigators
Study Chair: Gilles Salles, PhD CHU Lyon - Sud - LYSA
Study Chair: Loïc YSEBAERT, MD CHU de Toulouse LYSA
  More Information

Additional Information:
No publications provided

Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT01766583     History of Changes
Other Study ID Numbers: CLEAR
Study First Received: October 29, 2012
Last Updated: February 12, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes

Keywords provided by The Lymphoma Academic Research Organisation:
Open label, 3 + 3 dose escalation study followed by an expansion phase.

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014