Advanced Hematologic Malignancies, Leukemia, Preleukemia
Conditions
Keywords
Melphalan, Alemtuzumab, Clofarabine
Brief summary
This is a clinical research study designed to evaluate whether a conditioning regimen consisting of the combination of three drugs named melphalan, alemtuzumab and clofarabine supported by donor blood cells will result in rapid recovery and a high rate of long-lasting remissions in patients with leukemia, lymphoma and myeloma.
Interventions
PROCEDUREStem Cell Transplant
Infusion of donor, bone marrow and auto.
DRUGClofarabine
Clofarabine will be administered as a 2-hour IV infusion on Days 1 through 5 at approximately the same time everyday (4 dose levels).
DRUGMelphalan
Doses ranging from 100 to 140 mg/m2
DRUGCampath
20mg/d x5
Sponsors
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Relapsed or refractory acute myelogenous or lymphoid leukemia * Chronic myelogenous leukemia in accelerated phase or blast-crisis * Chronic myelogenous leukemia in second or subsequent chronic phase * Recurrent or refractory malignant lymphoma or Hodgkin's disease * Multiple myeloma at high risk for disease recurrence * Chronic lymphocytic leukemia, relapsed or with poor prognostic features * Other Myeloproliferative disorder (polycythemia vera, essential thrombocythemia, myelofibrosis) with poor prognostic features * Myelodysplastic syndromes (including PNH) with \> 5% blasts * Zubroid performance status \< 2 (See Appendix B) * Life expectancy is not severely limited by concomitant illness * Adequate cardiac and pulmonary function. Patients with decreased LVEF or PFTS will be evaluated by cardiology or pulmonary prior to enrollment on this protocol * Calculated Creatinine Clearance \> 50 ml/min * Serum bilirubin 2.0 mg/dl, SGPT \< 3x upper limit of normal * No evidence of chronic active hepatitis or cirrhosis * HIV-negative * Patient is not pregnant * Patient or guardian able to sign informed consent
Exclusion criteria
* Clinical progression
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Day 7 until Day 30 | Toxicity was scored according to NCI/CTC version 3 |
| Number of Participants With Hepatic Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Day 7 until Day 30 | Toxicity was scored according to NCI/CTC version 3 |
| Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Day 7 until Day 30 | Toxicity was scored according to NCI/CTC version 3 |
| Number of Participants With Skin Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Day 7 until Day 30 | Toxicity was scored according to NCI/CTC version 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 1 year | — |
| Progression-free Survival (PFS) | 1 year | Progression is defined from stem cell infusion to disease relapse, i.e., recurrence of hematologic malignancy and/or need for treatment after transplant for disease or death from any cause, whichever occurred first. |
| Treatment-related Mortality (TRM) | 1 year | — |
| Relapse Rate | 1 year | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clofarabine, Melphalan, and Alemtuzumab Clofarabine was initially administered IV infusion over 1 hour on days -7 through -3 (4 dose levels from 10 to 40 mg/m2); subsequently, the protocol was amended to infuse clofarabine over 3 hours. Melphalan (doses ranging from 100 to 140 mg/m2) was infused over 30 minutes on day -2. Alemtuzumab was administered at 20 mg IV infusion on day -7 through day -3 over 1 hour. | 82 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
Baseline characteristics
| Characteristic | Clofarabine, Melphalan, and Alemtuzumab |
|---|---|
| Age, Continuous | 54 years |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 62 / 82 |
| serious Total, serious adverse events | 44 / 82 |
Outcome results
Primary
Number of Participants With Hepatic Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation
Toxicity was scored according to NCI/CTC version 3
Time frame: Day 7 until Day 30
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Hepatic Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 1-2 | 48 participants |
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Hepatic Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 3-4 | 30 participants |
Primary
Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation
Toxicity was scored according to NCI/CTC version 3
Time frame: Day 7 until Day 30
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 1-2 | 12 participants |
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 3-4 | 7 participants |
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 5 | 7 participants |
Primary
Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation
Toxicity was scored according to NCI/CTC version 3
Time frame: Day 7 until Day 30
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 1-2 | 26 participants |
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 3-4 | 13 participants |
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 5 | 3 participants |
Primary
Number of Participants With Skin Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation
Toxicity was scored according to NCI/CTC version 3
Time frame: Day 7 until Day 30
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Skin Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 1-2 | 6 participants |
| Clofarabine, Melphalan, and Alemtuzumab | Number of Participants With Skin Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Grade 3-4 | 8 participants |
Secondary
Overall Survival (OS)
Time frame: 1 year
Population: 74 patients received the Maximum Tolerated Dose of clofarabine 40 mg/m2 IV daily x 5 days, melphalan 140 mg/m2 x 1 day, and alemtuzumab 20 mg IV daily x 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine, Melphalan, and Alemtuzumab | Overall Survival (OS) | 59 percentage of participants |
Secondary
Progression-free Survival (PFS)
Progression is defined from stem cell infusion to disease relapse, i.e., recurrence of hematologic malignancy and/or need for treatment after transplant for disease or death from any cause, whichever occurred first.
Time frame: 1 year
Population: 74 patients received the Maximum Tolerated Dose of clofarabine 40 mg/m2 IV daily x 5 days, melphalan 140 mg/m2 x 1 day, and alemtuzumab 20 mg IV daily x 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine, Melphalan, and Alemtuzumab | Progression-free Survival (PFS) | 45 percentage of participants |
Secondary
Relapse Rate
Time frame: 1 year
Population: 74 patients received the Maximum Tolerated Dose of clofarabine 40 mg/m2 IV daily x 5 days, melphalan 140 mg/m2 x 1 day, and alemtuzumab 20 mg IV daily x 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine, Melphalan, and Alemtuzumab | Relapse Rate | 29 percentage of participants |
Secondary
Treatment-related Mortality (TRM)
Time frame: 1 year
Population: 74 patients received the Maximum Tolerated Dose of clofarabine 40 mg/m2 IV daily x 5 days, melphalan 140 mg/m2 x 1 day, and alemtuzumab 20 mg IV daily x 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine, Melphalan, and Alemtuzumab | Treatment-related Mortality (TRM) | 26 percentage of participants |