Description:
Combined modality approach using Obitunuzumab and involved site low dose irradiation in early
stage nodal follicular lymphoma. Radiation dose will be adapted for low-responders.
Primary Objective:
Evaluation of the rate of metabolic CR after low-dose involved site radiotherapy in
combination with Gazyvaro (Obinutuzumab) in early stage nodal follicular lymphoma in order to
avoid conventional full dose IF radiotherapy.
Secondary Objective:
Efficacy and safety of a response adapted radiation dose treatment schedule.
Title
- Brief Title: Gazyvaro and Low Dose Radiotherapy in Early Stage Follicular Lymphoma
- Official Title: Therapy of Nodal Follicular Lymphoma (WHO Grade 1/2) in Clinical Stage I/II Using Response Adapted Involved Site Radiotherapy in Combination With Gazyvaro
Clinical Trial IDs
- ORG STUDY ID:
2016-002059-89
- NCT ID:
NCT03341520
Conditions
- Stage II Grade 1 Follicular Lymphoma
- Stage II Grade 2 Follicular Lymphoma
- Stage I Follicular Lymphoma Grade 1
- Stage II Follicular Lymphoma Grade 2
Interventions
Drug | Synonyms | Arms |
---|
Obinutuzumab Injection [Gazyva] | Gazyvaro | interventional arm |
Purpose
Combined modality approach using Obitunuzumab and involved site low dose irradiation in early
stage nodal follicular lymphoma. Radiation dose will be adapted for low-responders.
Primary Objective:
Evaluation of the rate of metabolic CR after low-dose involved site radiotherapy in
combination with Gazyvaro (Obinutuzumab) in early stage nodal follicular lymphoma in order to
avoid conventional full dose IF radiotherapy.
Secondary Objective:
Efficacy and safety of a response adapted radiation dose treatment schedule.
Detailed Description
Extended field or total nodal irradiation had been the gold standard for early stage
follicular lymphoma for a long time in Germany. An involved field (IF) irradiation has been
favored due to the toxicity of large field irradiation in other countries (e.g. USA).
However, smaller irradiation fields have been accompanied with an increased risk of
recurrence. A combination of involved field irradiation with the anti-CD20 antibody Rituximab
(MIR trial) has led to similar efficacy results compared to the large field irradiation but
with markedly reduced side effects.
Haas et al. showed in a prospective trial, that a low dose radiation therapy (LDRT) can lead
to a complete remission in up to 60% in follicular lymphoma. This is presumed to result from
immune modulatory effects induced by LDRT. The effectiveness of LDRT could also be
demonstrated in another prospective, randomized British trial (FORT trial: 2 x2 Gy vs. 12 x 2
Gy) with a CR rate of 40% after 2 x 2 Gy (60% after 12 x 2 Gy). Currently, it is unknown,
which patients need a higher radiation dose and which not.
A metabolic complete remission (CR) is an important prognostic marker for progression-free
survival. According to the results of the PRIMA trial, CR is a very strong predictive
parameter if the CR is established using FDG-PET.
In the present GAZAI trial, patients with early stage nodular follicular lymphoma will be
treated in a combined approach of immunotherapy with an anti-CD20 antibody and small field
(involved site) irradiation as in the MIR trial. In GAZAI, the fully humanized anti-CD20
antibody Obinutuzumab (GAZYVARO) will be used, which showed a high efficacy in combination
with bendamustin in patients with follicular lymphoma refractory to Rituximab (GADOLIN
trial). In addition, the radiation dose will be limited to 2 x2 Gy in responding patients. A
dose build-up to a total of 40 Gy (dose in the MIR trial) will be performed in case of
failure to achieve a complete CR based on a FDG-PET in week 18.
Primary endpoint of the trial is the rate of CR (based on FDG-PET/CT) after Obinutuzumab and
2x2 Gy IS radiotherapy in week 18. Secondary endpoints are the morphological CR rate in week
7, week 18 and month 6, the PFS, the toxicity, the recurrence rate, the recurrence pattern,
overall survival and quality of life.
Trial Arms
Name | Type | Description | Interventions |
---|
interventional arm | Experimental | Obinutuzumab Injection [Gazyva] 1000mg flat i.v. on week 1, 2, 3, 4, 8, 12, 16; Low dose radiation Therapy (LDRT) involved site 2 x 2 Gy in week 9 | - Obinutuzumab Injection [Gazyva]
|
Eligibility Criteria
Inclusion Criteria:
- Centrally reviewed CD20-positive follicular lymphoma grade 1/2 based on WHO
classification (2016)
- Untreated (radiation-, chemo- or immunotherapy) nodal lymphoma (including involvement
of Waldeyer´s ring)
- Age: ≥18 years
- ECOG: 0-2
- Stage: clinical stage I or II (Ann Arbor classification)
- Risk profile: Largest diameter of the lymphoma * 7 cm (sectional images)
- Written informed consent and willingness to cooperate during the course of the trial
- Adequate hematologic function (unless abnormalities are related to NHL), defined as
follows: Hemoglobin ≥ 9.0 g/dL; absolute neutrophil count ≥ 1.5 × 109/L, Platelet
count ≥ 75 × 109/L
- Capability to understand the intention and the consequences of the clinical trial
- Adequate contraception for men and women of child-bearing age during therapy and 18
months thereafter
- Patients with non-active hepatitis B infection (HBsAg neg/HBcAB pos/HBV DNA neg) under
1-year require prophylactic anti-viral therapy (e.g. Entecavir®) possible (see also
5.6. Prior and Concomitant Disease)
Exclusion Criteria:
- Extra nodal manifestation
- Secondary cancer in the patient's medical history (exclusion: basalioma, spinalioma,
melanoma in situ, bladder cancer T1a, non-metastasized solid tumor in constant
remission, which was diagnosed >3 years ago
- Concomitant diseases: congenital or acquired immune-deficiency syndromes, active
infections including viral hepatitis (serology positive for HBsAg or HBcAb in
combination positive HBV DNA), uncontrolled concomitant diseases including significant
cardiovascular or pulmonary disease (see also 5.6. Prior and Concomitant Disease)
- Severe psychiatric disease
- Pregnancy / lactation
- Known hypersensitivity against Gazyvaro (Obinutuzumab) or drugs with similar chemical
structure or any other additive of the pharmaceutical formula of the study drug
- Participation in another interventional trial or follow-up period of a competing trial
which can influence the results of this current trial
- Creatinine > 1.5 times the upper limit of normal (ULN) (unless creatinine clearance
normal), or calculated creatinine clearance < 40 mL/min
- AST or ALT > 2.5 × ULN
- Total bilirubin ≥ 1.5 × ULN
- INR > 1.5 × ULN
- PTT or aPTT > 1.5 × the ULN
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Rate of metabolic complete remission (CR) |
Time Frame: | week 18 |
Safety Issue: | |
Description: | rate of metabolic complete remission (CR) after low-dose involved site radiotherapy in combination with Obinutuzumab in patients with initially remaining PET positive lymphoma |
Secondary Outcome Measures
Measure: | Rate of morphologic complete remission (CR) |
Time Frame: | week 7, week 18, month 6 |
Safety Issue: | |
Description: | rate of morphologic complete remission (CR) after low-dose involved site radiotherapy in combination with Obinutuzumab in patients with initially remaining lymphoma |
Measure: | Progression free survival (PFS) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | PFS of all patients |
Measure: | Toxicity |
Time Frame: | Start until month 30 |
Safety Issue: | |
Description: | Common Toxicity Criteria (CTC) Toxicity |
Measure: | Overall survival (OS) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | OS of all patients |
Measure: | Relapse rate |
Time Frame: | start until month 30 |
Safety Issue: | |
Description: | Relapse rate of all patients |
Measure: | Quality of life (QoL) EORTC QLQ-C30 |
Time Frame: | Initially, week 18, month 12, month 24 |
Safety Issue: | |
Description: | QoL according EORTC QLQ-C30 |
Measure: | Minimal residual disease (MRD) response |
Time Frame: | initially, week 18, month 6, month 12, month 18, month 24 |
Safety Issue: | |
Description: | Minimal residual disease |
Measure: | Relapse pattern |
Time Frame: | start until month 30 |
Safety Issue: | |
Description: | Relapse pattern (e.g. out-field or in-field) of all relapses |
Measure: | Quality of life (QoL) FACT-Lymph25 |
Time Frame: | Initially, week 18, month 12, month 24 |
Safety Issue: | |
Description: | QoL according FACT-Lymph25 questionnaires |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Heidelberg University |
Last Updated
August 26, 2021