Multiple Myeloma, Plasma Cell Leukemia
Conditions
Keywords
Stage II/III Multiple Myeloma(within 10 months from diagnosis), high risk, relapse, persistent
Brief summary
Standard therapy for multiple myeloma (MM) usually includes an autologous bone marrow stem cell transplant - a procedure where the patient is treated with high dose chemotherapy and then their own (autologous) stem cells are transplanted back into their body. Patients with multiple myeloma and high risk genes, always relapse after an autologous transplant and often die within two years from the time of their transplant. A different type of transplant allogeneic) using donor cells, may work better for high-risk Multiple Myeloma, because the donor cells may help kill the lymphoid cancer cells. This study will investigate if a matched donor stem cell transplant using a newer, reduced toxicity, chemotherapy (Flu-Bu4) is a feasible option for patients with high risk, Multiple Myeloma.
Interventions
DRUGFludarabine/Busulfan x 4 days
* Fludarabine: 40 mg/m2/day in NS, administered IV over 30 minutes on days -5, -4, -3, and -2 pre-transplant. * Busulfan: 3.2 mg/kg IV daily in NS over 4 hours on days -5, -4, -3, and -2. The Fludarabine shall be administered prior to the Busulfan each day.
PROCEDUREstem cell transplant
Allogeneic, peripheral blood stem cell transplant
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Biologic high risk Multiple Myeloma: * Stage II/III Multiple Myeloma, any of: t(4; 14), t(14; 16),(14:20) by Fish; 17P- by conventional cytogenetics or Fish; ∆13 by conventional cytogenetics; Hypodiploidy by conventional cytogenetics. * Relapsed or persistent multiple myeloma after ASCT. * Persistent multiple myeloma, regardless of previous therapies. * Plasma cell leukemia, regardless of previous therapies. * Age up to 70 years old (less than 71 years old at the date of transplant admission). * Disease status: in CR, nCR, VGPR, PR or stable disease within 1 month of admission * Patients with non-secretory and oligosecretory disease are eligible if they meet certain criteria within 2 weeks prior to the transplant. * Specific renal, liver, cardiac, and pulmonary function requirements(all must be met within 30 days of transplant admission)
Exclusion criteria
* Persistent invasive infections, not controlled by antimicrobials. * HIV-1/HIV-2 or HTLV-1/HTLV-2 seropositivity. * Uncontrolled medical or psychiatric disorder. * No response or progressive disease at the time of transplantation. * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients Alive 1 Year Post Transplant | 1 Year | The primary objective is overall survival, one year from the time of transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients Free From Progression at 1 Year | 1 Year | One of the secondary outcomes that will be measured is progression free survival at 1 Year. Progressive Disease (PD) is defined as a \>25% increase in serum monoclonal paraprotein, a \>25% increase in 24-hour urinary light chain excretion, a \>25% increase in plasma cells in bone marrow aspirate, an increase in the size or the development of new bone lesions/soft tissue plasmacytomas, or the development of hypercalcemia. |
| Percentage of Patients With Treatment Related Mortality (TRM) | 100 days, one-year | — |
| Percentage of Patients With Acute and Chronic Graft Versus Host Disease (GVHD) | 100 days, 2 years | Incidence of acute (Stage II-IV and Stage III-IV) and chronic GVHD (any stage) were analyzed. Acute GVHD Grading: Stage II - Skin, 25-50% BSA (Body Surface Area); Liver, 3.1-6mg/dl bilirubin; Gut, 1000-1500ml/day diarrhea Stage III - Skin, generalized erythroderma; Liver, 6.1-15mg/dl bilirubin; Gut, \>1500ml/day diarrhea Stage IV - Skin, bullae; Liver, \>15mg/dl bilirubin; Gut, pain +/- ileus |
| Non Relapse Mortality (NRM) at 1 Year and 3 yearsThe Percentage of Deaths Not Attributable to Disease Relapse or Progression | 3 years | Non relapse mortality, defined as the percentage of deaths not attributable to disease relapse or progression at 1 year and at 3 years. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Flu-Bu4 Fludarabine Busulfan chemotherapy regimen(Flu-Bu4), followed by allogeneic stem cell transplant from best available, matched donor.
Fludarabine/Busulfan x 4 days:
Fludarabine: 40 mg/m2/day in NS, administered IV over 30 minutes on days -5, -4, -3, and -2 pre-transplant.
Busulfan: 3.2 mg/kg IV daily in NS over 4 hours on days -5, -4, -3, and -2.
The Fludarabine shall be administered prior to the Busulfan each day. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Flu-Bu4 |
|---|---|
| Age, Continuous | 54 years |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 22 |
| serious Total, serious adverse events | 13 / 22 |
Outcome results
Primary
The Percentage of Patients Alive 1 Year Post Transplant
The primary objective is overall survival, one year from the time of transplant.
Time frame: 1 Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Flu-Bu4 | The Percentage of Patients Alive 1 Year Post Transplant | 61 percentage of patients |
Secondary
Non Relapse Mortality (NRM) at 1 Year and 3 yearsThe Percentage of Deaths Not Attributable to Disease Relapse or Progression
Non relapse mortality, defined as the percentage of deaths not attributable to disease relapse or progression at 1 year and at 3 years.
Time frame: 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flu-Bu4 | Non Relapse Mortality (NRM) at 1 Year and 3 yearsThe Percentage of Deaths Not Attributable to Disease Relapse or Progression | NRM at 1 Year | 19 percentage of deaths |
| Flu-Bu4 | Non Relapse Mortality (NRM) at 1 Year and 3 yearsThe Percentage of Deaths Not Attributable to Disease Relapse or Progression | NRM at 3 Years | 29 percentage of deaths |
Secondary
Percentage of Patients With Acute and Chronic Graft Versus Host Disease (GVHD)
Incidence of acute (Stage II-IV and Stage III-IV) and chronic GVHD (any stage) were analyzed. Acute GVHD Grading: Stage II - Skin, 25-50% BSA (Body Surface Area); Liver, 3.1-6mg/dl bilirubin; Gut, 1000-1500ml/day diarrhea Stage III - Skin, generalized erythroderma; Liver, 6.1-15mg/dl bilirubin; Gut, \>1500ml/day diarrhea Stage IV - Skin, bullae; Liver, \>15mg/dl bilirubin; Gut, pain +/- ileus
Time frame: 100 days, 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flu-Bu4 | Percentage of Patients With Acute and Chronic Graft Versus Host Disease (GVHD) | Grade II-IV Acute GVHD | 48 percentage of participants |
| Flu-Bu4 | Percentage of Patients With Acute and Chronic Graft Versus Host Disease (GVHD) | Grade III-IV Acute GVHD | 23 percentage of participants |
| Flu-Bu4 | Percentage of Patients With Acute and Chronic Graft Versus Host Disease (GVHD) | Chronic GVHD | 55 percentage of participants |
Secondary
Percentage of Patients With Treatment Related Mortality (TRM)
Time frame: 100 days, one-year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Flu-Bu4 | Percentage of Patients With Treatment Related Mortality (TRM) | 9 percentage of patients |
Secondary
The Percentage of Patients Free From Progression at 1 Year
One of the secondary outcomes that will be measured is progression free survival at 1 Year. Progressive Disease (PD) is defined as a \>25% increase in serum monoclonal paraprotein, a \>25% increase in 24-hour urinary light chain excretion, a \>25% increase in plasma cells in bone marrow aspirate, an increase in the size or the development of new bone lesions/soft tissue plasmacytomas, or the development of hypercalcemia.
Time frame: 1 Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Flu-Bu4 | The Percentage of Patients Free From Progression at 1 Year | 40 percentage of patients |