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

NCT02962401 | Completed Phase 2 DMC

• 1 other identifier: RemodelWM3
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective national multicenter open label phase II Remodel WM3 trial

Conditions

Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  From date of registration until the date of first documented progression or date of death

  8 years

Secondary Outcomes (4)

• Overall response rates (ORR)

  Month 8

• Duration of response (RD)

  7 years and 4 months

• Time to treatment failure (TTF)

  through study completion, an average of 8 years

• Time to next treatment (TTNT)

  through study completion, an average of 8 years

Study Arms (1)

Idelalisib and Obinutuzumab

EXPERIMENTAL

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; Drug: Idelalisib

Interventions

Obinutuzumab DRUG

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

Also known as: GA101

Idelalisib and Obinutuzumab

Idelalisib DRUG

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

Also known as: Zydelig

Idelalisib and Obinutuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead

Study Sites (1)

Project manager

Tours, 37044, France

Location

Related Publications (2)

• Tomowiak C, Poulain S, Nudel M, Feugier P, Herbaux C, Mahe B, Morel P, Aurran T, Tournilhac O, Lepretre S, Assaad S, Villemagne B, Casasnovas O, Lhermitte A, Roos-Weil D, Torregrosa-Diaz J, Chevret S, Leblond V; on the behalf of the FILO group. Six-year follow-up of phase II study exploring chemo-free treatment association with idelalisib and obinutuzumab in symptomatic relapsed/ refractory patients with Waldenstrom's macroglobulinemia. Ann Hematol. 2025 Jan;104(1):685-690. doi: 10.1007/s00277-024-06076-1. Epub 2024 Nov 5.

  PMID: 39499299 DERIVED

• Tomowiak C, Poulain S, Herbaux C, Perrot A, Mahe B, Morel P, Aurran T, Tournilhac O, Lepretre S, Assaad S, Villemagne B, Casasnovas O, Nollet D, Roos-Weil D, Chevret S, Leblond V. Obinutuzumab and idelalisib in symptomatic patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood Adv. 2021 May 11;5(9):2438-2446. doi: 10.1182/bloodadvances.2020003895.

  PMID: 33961019 DERIVED

Related Links

• FILO internet site

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

obinutuzumab; idelalisib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Adeline LHERMITTE, Mrs

  French Innovative Leukemia Organisation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2016
• First Posted: November 11, 2016
• Study Start: March 7, 2017
• Primary Completion: August 31, 2020
• Study Completion: April 13, 2023
• Last Updated: August 29, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)