Mantle Cell Lymphoma
Conditions
Brief summary
This single arm study will evaluate the benefit of adding MabThera to standard induction chemotherapy in patients with newly diagnosed mantle cell lymphoma. The safety and tolerability of a MabThera-containing first line regimen will also be assessed. All patients will receive MabThera (375mg/m2 iv) every 3 weeks for 8 cycles, in combination with standard chemotherapy. The anticipated time on study treatment is 3-12 months, and the target sample size is \<100 individuals.
Interventions
DRUGrituximab [MabThera/Rituxan]
375mg/m2 iv every 3 weeks
DRUGFirst line chemotherapy
As prescribed
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* histologically-proven mantle cell lymphoma; * previously untreated disease at stage II, III and IV, requiring therapy.
Exclusion criteria
* known hypersensitivity reaction to rituximab, or known anti-murine antibody reactivity or known hypersensitivity to murine antibodies; * active malignancy other than mantle cell lymphoma within 5 years of start of study, with the exception of resected basal cell cancer, squamous cell cancer of the skin, or in situ cancer of the cervix; * serious disorders interfering with full standard dosing chemotherapy; * stage I disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Complete Remission (CR) (Including Unconfirmed CR [CR(u)]) or Partial Remission (PR) | Screening, Baseline (BL), every 21 days thereafter up to Week 27, every 3 months thereafter up to Month 24, Withdrawal Visit (4 weeks after discontinuation of study treatment) | CR was defined by: a) disappearance of clinical/radiographic evidence of disease, disease-related symptoms, and biochemical abnormalities; b) decrease in lymph nodes (LNs) greater than (\>) 1.5 centimeters (cm) in greatest transverse diameter (GTD) to less than (\<) 1.5 cm, a decrease in LNs 1.1 - 1.5 cm to 1 cm or 75 percent (%) decrease in sum of the products of GTD (SPD); c) non-palpable spleen, decreased size of enlarged organs, and disappearance of nodules; and d) disappearance of bone marrow (BM) infiltrate. CR(u) was defined as fulfilling a) and c), above, with greater than or equal to (≥) 1 of the following: a) \> 75% decrease in SPD of LNs \> 1.5 cm, and \> 75% decrease in SPD of previously confluent LNs; b) indeterminate BM, or c) confirmed CR. PR was defined by: a) 50% decrease in SPD of the 6 largest LNs; b) no increase in LNs, liver, or spleen size; c) ≥ 50% decrease in splenic and hepatic nodule SPDs; d) no measurable disease in other organs; and e) no new sites of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Screening, BL, every 21 days thereafter up to Week 27, every 3 months thereafter up to Month 24, Withdrawal Visit (4 weeks after discontinuation of study treatment) | PFS was defined as the median time, in months, from the date of study entry to disease progression, death due to mantle cell lymphoma, or last contact. Progressive disease (PD) was defined by: a) 50% increase from nadir in the SPD of any previously identified abnormal LN, or b) appearance of any new lesion during or at the end of treatment. The 95% confidence interval (CI) was estimated using Kaplan-Meier methodology. |
| Event Free Survival (EFS) | Screening, BL, every 21 days thereafter up to Week 27, every 3 months thereafter up to Month 24, Withdrawal Visit (4 weeks after discontinuation of study treatment) | EFS was defined as the median time, in months, from the date of study entry disease progression, relapse, secondary malignancy, death or last contact. Relapse was defined by: a) appearance of any new lesion or a ≥ 50% increase in size of previously involved sites, or b) ≥ 50% increase in GTD of any previously identified LN \>1 cm in short axis or in the SPD of more than one LN. The 95% CI was estimated using Kaplan-Meier methodology. |
Countries
Hungary
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab + Chemotherapy Participants received rituximab, 375 mg/m\^2, IV, on Day 1 of Cycles 1-8 (21-day cycle). Participants also received 1 of the following chemotherapies: CHOP, Cycles 1-8: cyclophosphamide, 750 mg/m\^2, IV, doxorubicin, 50 mg/m\^2, IV, or epirubicin, 70 mg/m\^2, IV, vincristine, 1.4 mg/m\^2, IV, on Day 1 of Cycles 1-8, and methylprednisolone, 16 mg/d, IV or PO, on Days 1-5. OR Hyper-CVAD/M-A, Cycles 1, 3, 5, and 7: cyclophosphamide, 300 mg/m\^2, IV, q12h on Days 2-4; mesna, 600 mg/m\^2, IV, 1 hour before the start of cyclophosphamide on Days 2-4; doxorubicin, 50 mg/m\^2, IV, or epirubicin, 70 mg/m\^2, IV, on Day 5; vincristine, 1.4 mg/m\^2, IV, on Days 5 and 12; and dexamethasone, IV or PO, 40 mg/day on Days 2-5 and Days 12-15. Hyper-CVAD/M-A, Cycles 2, 4, 6, and 8: methotrexate, 200 mg/m\^2, IV, followed by 800 mg/m\^2, IV, on Day 2; cytarabine, 3000 mg/m\^2, IV over 2 hours, q12h on Day 3 (2 doses) or Days 3-4 (4 doses). | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up Period | Death | 5 |
| Follow-up Period | Lost to Follow-up | 2 |
| Follow-up Period | Physician Decision | 9 |
| Follow-up Period | Protocol Violation | 1 |
| Induction Treatment Period | Adverse Event | 3 |
| Induction Treatment Period | Death | 3 |
| Induction Treatment Period | Non-compliance | 1 |
| Induction Treatment Period | Physician Decision | 9 |
Baseline characteristics
| Characteristic | Rituximab + Chemotherapy |
|---|---|
| Age, Continuous | 70.20 years |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 48 |
| serious Total, serious adverse events | 25 / 48 |
Outcome results
Primary
Number of Participants Achieving Complete Remission (CR) (Including Unconfirmed CR [CR(u)]) or Partial Remission (PR)
CR was defined by: a) disappearance of clinical/radiographic evidence of disease, disease-related symptoms, and biochemical abnormalities; b) decrease in lymph nodes (LNs) greater than (\>) 1.5 centimeters (cm) in greatest transverse diameter (GTD) to less than (\<) 1.5 cm, a decrease in LNs 1.1 - 1.5 cm to 1 cm or 75 percent (%) decrease in sum of the products of GTD (SPD); c) non-palpable spleen, decreased size of enlarged organs, and disappearance of nodules; and d) disappearance of bone marrow (BM) infiltrate. CR(u) was defined as fulfilling a) and c), above, with greater than or equal to (≥) 1 of the following: a) \> 75% decrease in SPD of LNs \> 1.5 cm, and \> 75% decrease in SPD of previously confluent LNs; b) indeterminate BM, or c) confirmed CR. PR was defined by: a) 50% decrease in SPD of the 6 largest LNs; b) no increase in LNs, liver, or spleen size; c) ≥ 50% decrease in splenic and hepatic nodule SPDs; d) no measurable disease in other organs; and e) no new sites of disease.
Time frame: Screening, Baseline (BL), every 21 days thereafter up to Week 27, every 3 months thereafter up to Month 24, Withdrawal Visit (4 weeks after discontinuation of study treatment)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab + Chemotherapy | Number of Participants Achieving Complete Remission (CR) (Including Unconfirmed CR [CR(u)]) or Partial Remission (PR) | CR | 19 participants |
| Rituximab + Chemotherapy | Number of Participants Achieving Complete Remission (CR) (Including Unconfirmed CR [CR(u)]) or Partial Remission (PR) | PR | 8 participants |
Secondary
Event Free Survival (EFS)
EFS was defined as the median time, in months, from the date of study entry disease progression, relapse, secondary malignancy, death or last contact. Relapse was defined by: a) appearance of any new lesion or a ≥ 50% increase in size of previously involved sites, or b) ≥ 50% increase in GTD of any previously identified LN \>1 cm in short axis or in the SPD of more than one LN. The 95% CI was estimated using Kaplan-Meier methodology.
Time frame: Screening, BL, every 21 days thereafter up to Week 27, every 3 months thereafter up to Month 24, Withdrawal Visit (4 weeks after discontinuation of study treatment)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab + Chemotherapy | Event Free Survival (EFS) | 40.049 months |
Secondary
Progression Free Survival (PFS)
PFS was defined as the median time, in months, from the date of study entry to disease progression, death due to mantle cell lymphoma, or last contact. Progressive disease (PD) was defined by: a) 50% increase from nadir in the SPD of any previously identified abnormal LN, or b) appearance of any new lesion during or at the end of treatment. The 95% confidence interval (CI) was estimated using Kaplan-Meier methodology.
Time frame: Screening, BL, every 21 days thereafter up to Week 27, every 3 months thereafter up to Month 24, Withdrawal Visit (4 weeks after discontinuation of study treatment)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab + Chemotherapy | Progression Free Survival (PFS) | 30.456 months |