Mantle Cell Lymphoma
Conditions
Keywords
Newly diagnosed
Brief summary
Mantle cell lymphoma (MCL) is not curable with conventional therapy. This study sought to improve upon standard of care in newly diagnosed, untreated MCL patients who were transplant-eligible using drugs already established as active in MCL. The combination of Rituximab-Bendamustine followed by Rituximab-Cytarabine (RB/RC) was expected to maximize pre-ASCT complete response (CR) rate compared to historical rates approximating 55% with tolerable toxicity.
Detailed description
This was a PII single-arm design to determine whether the regimen looked promising for further study. Primary Objective • To evaluate the efficacy of an alternating regimen of Rituximab-Bendamustine and Rituximab-Cytarabine (RB/RC) using the CR/Cru rate. Secondary Objectives * To assess safety. * To estimate the rate of complete remission (CR), unconfirmed CR (CRu), partial remission (PR), stable disease (SD) and progressive disease (PD). * To estimate the rate of successful stem cell mobilization after RB/RC in responding patients. * To estimate the proportion of patients who can successfully complete the regimen and proceed to autologous stem cell transplantation (ASCT). * To estimate the rate of neutrophil and platelet engraftment after ASCT. * To estimate the CR/CRu and PR rate for patients with blastoid variant MCL. * To estimate the rate of minimal residual disease (MRD)-negativity at treatment completion.
Interventions
DRUGRituximab
DRUGBendamustine
DRUGCytarabine
Sponsors
Christine Ryan
Beth Israel Deaconess Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Mandatory pathologic review of the diagnostic specimen(s) at Brigham and Women's Hospital or Massachusetts General Hospital * Measurable disease * Candidate for ASCT
Exclusion criteria
* Prior anti-lymphoma therapy * Pregnant or breastfeeding * Hypersensitivity to rituximab * Uncontrolled intercurrent illness * Receiving other study agents * HIV positive on combination antiretroviral therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission (CR) Rate After 6 Cycles | Disease was assessed after three- and six-cycles of therapy, up to approximately 25 weeks. All patients completed 6 cycles of therapy with a cycle duration of 28 days. | The CR rate is defined as the proportion of patients who after 6 cycles of therapy achieve complete remission based on the International Working Group (IWG) Criteria (Cheson et al, 1999), using CT scans. CR or CRu (CR unconfirmed) by CT scans was defined by standard IWG criteria, ie resolution of all abnormal adenopathy and organomegaly, and clearance of marrow disease when present at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1 Year Progression-Free Survival | Disease was assessed after three- and six-cycles of therapy and in long-term follow-up per standard practice every 6 months until the earliest of relapse, death or 5 years. Median follow-up in this study cohort was 13 months. | 1-year progression-free survival is the probability of patients remaining alive and progression-free at 1 year from study entry estimated using Kaplan-Meier methods. Disease progression was based on the International Working Group (IWG) Criteria (Cheson et al, 1999). |
| Autologous Stem Cell Transplant (ASCT) Rate | All patients were followed for continuation to ASCT upon completion of induction therapy. Patients usually proceed to ASCT within 3 months of completing induction. | ASCT rate is the proportion of patients who completed therapy and proceeded to autologous stem cell transplant (ASCT) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORChristine Ryan, MD
Dana-Farber Cancer Institute
Participant flow
Recruitment details
Patients enrolled from August 2012 through March 2014.
Participants by arm
| Arm | Count |
|---|---|
| RB/RC Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to:
1. 2 g/m2 for age \>60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity;
2. 1.5 g/m2 for age \>60 years old AND creatinine 114.9-176.8 lmol/l, or for age \>60 years old AND pre-existing neurotoxicity;
3. 1 g/m2 for age \> 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | RB/RC |
|---|---|
| Age, Continuous | 57 years |
| MIPI at Diagnosis High | 2 Participants |
| MIPI at Diagnosis Intermediate | 5 Participants |
| MIPI at Diagnosis Low | 16 Participants |
| Region of Enrollment United States | 23 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 15 / 23 |
Outcome results
Primary
Complete Remission (CR) Rate After 6 Cycles
The CR rate is defined as the proportion of patients who after 6 cycles of therapy achieve complete remission based on the International Working Group (IWG) Criteria (Cheson et al, 1999), using CT scans. CR or CRu (CR unconfirmed) by CT scans was defined by standard IWG criteria, ie resolution of all abnormal adenopathy and organomegaly, and clearance of marrow disease when present at baseline.
Time frame: Disease was assessed after three- and six-cycles of therapy, up to approximately 25 weeks. All patients completed 6 cycles of therapy with a cycle duration of 28 days.
Population: The analysis dataset is comprised of all enrolled patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RB/RC | Complete Remission (CR) Rate After 6 Cycles | .96 proportion of participants |
Secondary
1 Year Progression-Free Survival
1-year progression-free survival is the probability of patients remaining alive and progression-free at 1 year from study entry estimated using Kaplan-Meier methods. Disease progression was based on the International Working Group (IWG) Criteria (Cheson et al, 1999).
Time frame: Disease was assessed after three- and six-cycles of therapy and in long-term follow-up per standard practice every 6 months until the earliest of relapse, death or 5 years. Median follow-up in this study cohort was 13 months.
Population: The analysis dataset is comprised of all enrolled patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RB/RC | 1 Year Progression-Free Survival | .96 probability |
Secondary
Autologous Stem Cell Transplant (ASCT) Rate
ASCT rate is the proportion of patients who completed therapy and proceeded to autologous stem cell transplant (ASCT)
Time frame: All patients were followed for continuation to ASCT upon completion of induction therapy. Patients usually proceed to ASCT within 3 months of completing induction.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RB/RC | Autologous Stem Cell Transplant (ASCT) Rate | .91 proportion of participants |