Refractory Multiple Myeloma, Stage III Multiple Myeloma, Stage II Multiple Myeloma, Stage I Multiple Myeloma
Conditions
Brief summary
This phase II trial studies the effectiveness of melphalan, peripheral stem cell transplantation, and interleukin-2 followed by interferon alfa in treating patients who have advanced multiple myeloma (MM). Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Interleukin-2 (IL2) may stimulate a person's white blood cells to kill multiple myeloma cells. Interferon alfa may interfere with the growth of cancer cells
Detailed description
PRIMARY OBJECTIVES: I. Evaluate initial response to therapy, time to disease progression, and overall survival in MM patients treated with melphalan, IL2- incubated peripheral blood stem cells, and sequential IL2. SECONDARY OBJECTIVES: I. Evaluate grade 3-4 toxicities encountered by younger (\< 56 years old) and older (\>56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2. OUTLINE: Patients receive melphalan intravenously (IV) over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa subcutaneously (SC) 3 times a week in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGmelphalan
Given IV
BIOLOGICALrecombinant interferon alfa
Given SC
BIOLOGICALaldesleukin
Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
PROCEDUREin vitro-treated peripheral blood stem cell transplantation
Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer 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
* Patient must be less than 70 years old * Patients with advanced Multiple Myeloma that meet the eligibility requirements for mobilization/debulking with Cytoxan/VP-16/G-CSF, Cytoxan/Taxol/G-CSF, or Cytoxan/G-CSF (according to protocol 506.03); if clinically indicated a lower dose of cytoxan than 4g/m2 may be used for mobilization based on the attending's discretion; also, if the patients had previously collected PBSC of sufficient number in the past and meet the other eligibility requirements, they may be entered on this study after approval by the PI * Patients with advanced Multiple Myeloma that have an identical syngeneic twin for donation of PBSCs * Patients have advanced Multiple Myeloma if they were diagnosed initially with stage II or III disease or had stage I disease that progressed after initial therapy or failed to respond to therapy * Syngeneic Donor Inclusion: * Donor and patient have adequate documentation that donor and recipient are syngeneic; including ABO typing, HLA typing and VNTR studies * Donor \> 20 kg * Donor meets eligibility to donate according to Standard Practice Guidelines
Exclusion criteria
* Patient's age \>= 70 * Karnofsky score less than 80 * A left ventricular ejection fraction less than 50%; Patients with congestive heart disease, history of myocardial infarction (MI), coronary artery disease or any arrhythmia history * Total bilirubin \> 1.5 mg/ml (unless history of Gilbert's disease) * Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) \> 2 x upper limit of normal * Estimated creatinine clearance \< 60 ml/min or creatinine serum \> 2.0 mg/dl * Pregnancy * Seropositivity for human immunodeficiency virus * Patients who cannot give informed consent * Secondary malignancies other than basal cell carcinoma of the skin or carcinoma in situ within the last five years * History of seizures or requirement for medicines, such as haldol, for controlling mental disorders * Concurrent need for corticosteroid therapy * Active connective tissue disease * Pleural effusion, pericardial effusion or ascites * Patients allergic to gentamicin * Patients with positive PCR for hepatitis C or hepatitis B * Patients with hypersensitivity to E. coli - derived preparations * Patients with systemic infection at time of IL2 therapy * Patients who previously have had more than 50% of their pelvic area irradiated * Patients with pulmonary function tests that show diffusion capacity (corrected) \< 60%, and/or forced expiratory volume in 1 second (FEV1) \< 65% of predicted
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 12.9 Median Years | Overall survival in Multiple Myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2 and interferon maintenance. |
| Initial Response to Therapy | Evaluated at Day +84-90 Post-Transplant | Evaluate initial response to therapy (complete remission, partial remission, stable response, or progression of disease) |
| Time to Disease Progression | 12.9 years (median) | — |
| Proportion of Patients Alive and in Remission | 12.9 Median Years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients <56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity | First 100 days post-transplant | Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by younger (\< 56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2. |
| Number of Patients ≥56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity | First 100 days post-transplant | Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by older (≥56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Immunotherapy Treatment Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity.
melphalan: Given IV
recombinant interferon alfa: Given SC
aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Immunotherapy Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Age, Continuous | 53.56 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 27 / 36 |
| other Total, other adverse events | 0 / 36 |
| serious Total, serious adverse events | 10 / 36 |
Outcome results
Primary
Initial Response to Therapy
Evaluate initial response to therapy (complete remission, partial remission, stable response, or progression of disease)
Time frame: Evaluated at Day +84-90 Post-Transplant
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Immunotherapy Treatment | Initial Response to Therapy | Patients in Complete Remission | 15 Participants |
| Immunotherapy Treatment | Initial Response to Therapy | Patients in Partial Remission | 8 Participants |
| Immunotherapy Treatment | Initial Response to Therapy | Patients with Stable resposne | 10 Participants |
| Immunotherapy Treatment | Initial Response to Therapy | Patients with Disease Progression | 3 Participants |
Primary
Overall Survival
Overall survival in Multiple Myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2 and interferon maintenance.
Time frame: 12.9 Median Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunotherapy Treatment | Overall Survival | 9 Participants |
Primary
Proportion of Patients Alive and in Remission
Time frame: 12.9 Median Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunotherapy Treatment | Proportion of Patients Alive and in Remission | 4 Participants |
Primary
Time to Disease Progression
Time frame: 12.9 years (median)
Population: Out of 36 patients, 30 have relapsed and they are used to determine this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Immunotherapy Treatment | Time to Disease Progression | 1.61 years |
Secondary
Number of Patients <56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity
Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by younger (\< 56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.
Time frame: First 100 days post-transplant
Population: Of the 36 patients, 20 patients were \<56 years old and these 20 patients are used to determine this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunotherapy Treatment | Number of Patients <56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity | 1 Participants |
Secondary
Number of Patients ≥56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity
Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by older (≥56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.
Time frame: First 100 days post-transplant
Population: Of the 36 patients, 16 patients were ≥56 years old and these 16 are used to determine this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunotherapy Treatment | Number of Patients ≥56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity | 0 Participants |