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Efficacity of Idelalisib and Obinutuzumab in Patient With Relapsed Refractory Waldenstrom's Macroglobulinemia (RemodelWM3)

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02962401
Recruitment Status : Active, not recruiting
First Posted : November 11, 2016
Last Update Posted : September 3, 2018
Sponsor:
Information provided by (Responsible Party):
French Innovative Leukemia Organisation

Brief Summary:
Prospective national multicenter open label phase II Remodel WM3 trial

Condition or disease Intervention/treatment Phase
Waldenstrom Macroglobulinemia Drug: Obinutuzumab Drug: Idelalisib Phase 2

Detailed Description:
An Open Label non-randomized Phase II Study exploring chemo-free treatment association with Idelalisib and Obinutuzumab in Patient with relapsed refractory Waldenstrom's Macroglobulinemia

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Non-randomized Phase II Study Exploring "Chemo-free " Treatment Association With Idelalisib + Obinutuzumab in Patient With Relapsed/Refractory Waldenstrom's Macroglobulinemia
Actual Study Start Date : March 7, 2017
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2025


Arm Intervention/treatment
Experimental: Idelalisib and Obinutuzumab

6 cycles of Idelalisib and Obinutuzumab

Cycle 1 :

Idelalisib 150 mg x 2 p.o. day 1 to 28 Obinutuzumab 1000mg I.V. (2 parts) 100mg day 1 and 900mg day 2 day 1, 8 and 15

Cycle 2 - 6 :

Idelalisib 150 mg x 2 p.o. day 1 to 28 Obinutuzumab 1000mg I.V. day 1

Consolidation Idelalisib alone 150 mg twice a day until day 672 = 2 years after the beginning of the treatment

Drug: Obinutuzumab

6 cycles every 28 days Cycle 1 :Obinutuzumab 1000mg I.V.(2 parts) 100mg day 1 and 900mg day 2 day 1, 8 and 15

Cycle 2 - 6 :

Obinutuzumab 1000mg I.V.day 1

Other Name: GA101

Drug: Idelalisib

6 cycles every 28 days

Cycle 1 :

Idelalisib 150 mg x 2 p.o. day 1 to 28 Cycle 2 - 6 Idelalisib 150 mg x 2 p.o. day 1 to 28 Consolidation Idelalisib alone 150 mg twice a day until day 672 = 2 years after the beginning of the treatment

Other Name: Zydelig




Primary Outcome Measures :
  1. Progression free survival [ Time Frame: 8 years ]
    From date of registration until the date of first documented progression or date of death


Secondary Outcome Measures :
  1. Overall response rates (ORR) [ Time Frame: Month 8 ]
    treatment response

  2. Duration of response (RD) [ Time Frame: 7 years and 4 months ]
    from end of induction to the date of progression, relapse or death

  3. Time to treatment failure (TTF) [ Time Frame: through study completion, an average of 8 years ]
    time from start of induction to stable disease, progression or death from any cause

  4. Time to next treatment (TTNT) [ Time Frame: through study completion, an average of 8 years ]
    time from start of induction day 1 cycle 1 to time of the next treatment for progression or relapse



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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:

  • Age 18 years or older
  • Confirmed CD20 positive WM, according to the recommendations of the 2nd Workshop on WM.
  • Presence of at least one criterion for initiation of therapy, according to the 2nd Workshop on WM.
  • Recurrent fever, night sweats, weight loss, fatigue
  • Hyperviscosity
  • Lympadenopathy which is either symptomatic or bulky more or equal to 5cm in maximum diameter
  • Symptomatic hepatomegaly and/or splenomegaly
  • Symptomatic organomegaly and/or organ or tissue infiltration
  • Peripheral neuropathy due to WM
  • Symptomatic cryoglobulinemia
  • Cold agglutinin anemia
  • Immune hemolytic anemia and/or thrombocytopenia
  • Nephropathy related to WM
  • Amyloidosis related to WM
  • Hemoglobin less or equal than 10g dL
  • Platelet count less than 100 109 L
  • Prior treatment for WM comprising at least one regimen containing a therapeutic anti CD20 monoclonal antibody rituximab administered for more or equal than 2 doses of antibody treatment and or a therapeutic chemotherapy, alkylating agent, purine analogue, bendamustine administered for more or equal than 2 cycles of treatment
  • Patients may be either relapsing progressing at least 6 months after the last administration of first line or subsequent treatment or refractory progressing on or within 6 months of first line or subsequent treatment
  • Number of prior regimens per lines 1 to 3
  • Life expectancy more than 3 months.
  • ECOG less or equal than 2.
  • Meet the following pretreatment laboratory criteria at the screening visit conducted within 28 days of study enrollment:

    • ASAT 2.5 times the upper limit of institutional laboratory normal value.
    • ALAT 2.5 times the upper limit of institutional laboratory normal value.
    • Total bilirubin 1.5 times the upper limit of institutional laboratory normal value unless clearly related to the disease or Gilbert syndrome
    • Calculated or measured creatinin clearance by MDRD 40 mL minute.
  • Premenopausal fertile females must agree to use a highly effective method of birth control for the duration of the therapy up to 6 months after end of therapy.
  • A highly effective method of birth control is defined as those which result in a low failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.
  • Men must agree not to father a child for the duration of therapy and 6 months after and must agree to advice a female partner to use a highly effective method of birth control.
  • Voluntary written informed consent before carrying out any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

  • Prior treatment with phosphatidylinositol 3 kinase PI3K inhibitors including idelalisib or GA101
  • History of anaphylactic reaction following exposure to humanized monoclonal antibodies
  • Previous allogeneic transplantation
  • Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study
  • History of other malignancy or chemotherapy radiotherapy for any neoplastic disease other than WM prior to the study.

    • EXCEPTION: History of malignancy except basal cell carcinoma of the skin, in situ carcinoma of breast or cervix treated surgically with curative intent, or any malignancy that has been in CR for 5 years at minimum, or as deemed appropriate for inclusion in the trial as per approval by the investigator
  • Medical condition requiring the long-term estimated to be more than one month use of oral corticosteroids.
  • Patients with signs of bacterial, viral or fungal infection
  • Preexisting hepatic enzyme elevation ASAT, ALAT
  • CMV PCR or antigenemia testing positive
  • Known history of drug induced liver injury, chronic active hepatitis C HCV, chronic active hepatitis B HBV, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension
  • HIV antibody positive
  • Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb): Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU). Patients with positive serology should be referred to a hepatologist or gastroenterologist before start of treatment and should be monitored and managed following local standards to prevent hepatitis reactivation. Furthermore transaminases and HBV DNA quantification must be tested at weeks 4 and 8 after treatment start. Then transaminases must be tested at week 12 of treatment start.
  • Preexisting pulmonary disease
  • Known history of drug induced pneumonitis
  • On-going inflammatory bowel disease
  • Women who are pregnant. Women who are breast-feeding and do not consent to discontinue breast-feeding Women of childbearing age who are not willing to use effective anti-conceptive methods for the duration of the study and 6 months after end of therapy
  • Concurrent severe diseases which exclude the administration of therapy:
  • Heart insufficiency NYHA grade III IV, LVEF < 50% and or RF <30%, myocardial infarction within the past 6 months prior to study
  • Severe chronic obstructive lung disease with hypoxemia
  • Severe diabetes mellitus
  • Hypertension difficult to control
  • Cerebral dysfunction
  • Richter's syndrome
  • Cardiac amyloidosis
  • Any of the following laboratory abnormalities, if not related to lymphoma:
  • Absolute neutrophils count <1.5 x 109/L if not result of a bone marrow infiltration Platelet count <75 x 109/L if not result of a bone marrow infiltration.
  • Central Nervous System involvement by lymphoma
  • Vaccination with live vaccines within 28 days prior to study entry
  • Hypersensitivity to the active substance or to any of the excipients listed on part 6.1 of GAZYVARO and ZYDELIG SmCP
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation
  • Patient with mental deficiency preventing proper understanding of the requirements of treatment
  • Person major under law control.

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): NCT02962401


Locations
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France
Project manager
Tours, France, 37044
Sponsors and Collaborators
French Innovative Leukemia Organisation
Investigators
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Study Director: Delphine NOLLET, Mrs French Innovative Leukemia Organisation

Additional Information:
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Responsible Party: French Innovative Leukemia Organisation
ClinicalTrials.gov Identifier: NCT02962401     History of Changes
Other Study ID Numbers: RemodelWM3
First Posted: November 11, 2016    Key Record Dates
Last Update Posted: September 3, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: E CRF

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Idelalisib
Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Obinutuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action