A Phase 2 interventional study of Cyclophosphamide and Methotrexate in Leukemia, sponsored by Eastern Cooperative Oncology Group. Terminated at 68 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-07-05.
Sponsored by Eastern Cooperative Oncology Group · Phase 2, Interventional, and Treatment
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of methotrexate with or without cyclophosphamide in treating patients who have lymphocytic leukemia with neutropenia or anemia.
LGL leukemia is characterized by clonal expansion of cytotoxic T cells. Prominent clinical features include neutropenia, anemia, and rheumatoid arthritis. The terminal effector memory phenotype (CD3+/CD8+/CD57+/CD45RA+/CD62L-) of leukemic LGL suggest a pivotal chronic antigen driven immune response. LGL survival is then promoted by PDGF and IL-15, resulting in global dysregulation of apoptosis and resistance to normal pathways of activation-induced death. These pathogenic features explain why treatment of LGL leukemia is based on immunosuppression therapy. However, no standard therapy has been established due to the absence of large prospective trials.
Oral low dose MTX has been shown to be efficacious in the treatment of neutropenia. However, response to MTX is slow, requiring several months for the neutrophil count to increase above 500/mm3. Also, complete clinical remission may not be achieved until after one year of MTX therapy. Oral Cy has been the primary drug used for the treatment of severe transfusion-dependent anemia. Beneficial clinical effects are seen despite this treatment having no apparent effect on the abnormal LGL clone. Normal hematocrits are maintained after cessation of Cy and these results contrast the effects seen with MTX, in which clinical remissions are often associated with the disappearance of the clone.
This phase II trial undertaken by the Eastern Cooperative Group (ECOG) was initiated to investigate the mechanism of treatment response in patients with LGL leukemia, who need treatment for anemia or neutropenia.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 59 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →Eastern Cooperative Oncology Group is the lead sponsor of 173 studies on the registry; 7 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 5 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion:
Note: to be eligible for step 2 of this study, patients were required to have no response after at least 4 months of methotrexate treatment.
MTX given orally at 10 mg/m2 in divided doses once weekly. Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days. Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule.
Drug: Cyclophosphamide · Drug: Methotrexate · Drug: Prednisone
Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule. In patients showing a partial response, but not a CR, the maximum period of therapy was 1 year.
Initial treatment consisted of MTX given orally at 10 mg/m2 in divided doses once weekly.
Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days.
Proportion of Patients With Complete or Partial Response to Treatment With MTX
We will report the overall response rate below. Complete remission requires that all of the following be present for at least four weeks: The patient must have a normal CBC including neutrophil count \> 1500/mm3, lymphocyte count\< 4000/mm3, hemoglobin \> 11 g/dl, and platelet count \> 100,000/mm3. In addition, the patient must have a normal LGL count. A complete response will be attained if CD8+ cells were less than 760/mm³. A partial response will be defined as achievement of any one of the following in the absence of CR. The response must last for at least four weeks:In patients being treated for severe neutropenia (less than 500 neutrophils/mm3) an improvement to over 500 neutrophils/mm3 will be considered a partial response, as long as that improvement represents at least a 50% improvement.
Time frame: Assessed during the first 4 months, then at least every three months for two years. Then every six months until five years after study entry, and every 12 months thereafter until full study stop date.
Proportion of Patients With Complete or Partial Response to Treatment of CY Among Patients Failing to Respond to MTX
We will report the overall response rate below. Complete remission requires that all of the following be present for at least four weeks: The patient must have a normal CBC including neutrophil count \> 1500/mm3, lymphocyte count\< 4000/mm3, hemoglobin \> 11 g/dl, and platelet count \> 100,000/mm3. In addition, the patient must have a normal LGL count. A complete response will be attained if CD8+ cells were less than 760/mm³. A partial response will be defined as achievement of any one of the following in the absence of CR. The response must last for at least four weeks:In patients being treated for severe neutropenia (less than 500 neutrophils/mm3) an improvement to over 500 neutrophils/mm3 will be considered a partial response, as long as that improvement represents at least a 50% improvement.
Time frame: Assessed during the first 4 months of treatment and followed until reaching full study stop date
This study accrued 59 patients between July 16, 1999 and March 24, 2009. The first patient was accrued on September 15, 1999. The study terminated with 59 patients on March 24, 2009 due to slower than expected accrual.
| Milestone | Methotrexate | Cyclophosphomide |
|---|---|---|
| Started | 55 | 0 |
| Completed | 55 | 0 |
| Not completed | 0 | 0 |
| Milestone | Methotrexate | Cyclophosphomide |
|---|---|---|
| Started | 0 | 16 |
| Completed | 0 | 16 |
| Not completed | 0 | 0 |
We will report the overall response rate below. Complete remission requires that all of the following be present for at least four weeks: The patient must have a normal CBC including neutrophil count \> 1500/mm3, lymphocyte count\< 4000/mm3, hemoglobin \> 11 g/dl, and platelet count \> 100,000/mm3. In addition, the patient must have a normal LGL count. A complete response will be attained if CD8+ cells were less than 760/mm³. A partial response will be defined as achievement of any one of the following in the absence of CR. The response must last for at least four weeks:In patients being treated for severe neutropenia (less than 500 neutrophils/mm3) an improvement to over 500 neutrophils/mm3 will be considered a partial response, as long as that improvement represents at least a 50% improvement.
| proportion of participants | Methotrexate |
|---|---|
| Proportion of Patients With Complete or Partial Response to Treatment With MTX | 0.39 (0.26 to 0.53) |
We will report the overall response rate below. Complete remission requires that all of the following be present for at least four weeks: The patient must have a normal CBC including neutrophil count \> 1500/mm3, lymphocyte count\< 4000/mm3, hemoglobin \> 11 g/dl, and platelet count \> 100,000/mm3. In addition, the patient must have a normal LGL count. A complete response will be attained if CD8+ cells were less than 760/mm³. A partial response will be defined as achievement of any one of the following in the absence of CR. The response must last for at least four weeks:In patients being treated for severe neutropenia (less than 500 neutrophils/mm3) an improvement to over 500 neutrophils/mm3 will be considered a partial response, as long as that improvement represents at least a 50% improvement.
| proportion of participants | Cyclophosphamide (Cy) |
|---|---|
| Proportion of Patients With Complete or Partial Response to Treatment of CY Among Patients Failing to Respond to MTX | 0.64 (0.35 to 0.87) |
Collected over Assessed every 30 days while on treatment and for 30 days after the end of treatment.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Methotrexate | — | 56/59 (94.9%) | 56/59 (94.9%) |
| Cyclophosphamide | — | 8/16 (50%) | 6/16 (37.5%) |
| Event | Methotrexate | Cyclophosphamide |
|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 30/59 | 6/16 |
| LymphopeniaBlood and lymphatic system disorders | 5/59 | 7/16 |
| LeukopeniaBlood and lymphatic system disorders | 10/59 | 6/16 |
| AnemiaBlood and lymphatic system disorders | 13/59 | 5/16 |
| HyperglycemiaBlood and lymphatic system disorders | 6/59 | 2/16 |
| Infection with grade 3 or 4 neutropeniaInfections and infestations | 6/59 | 0/16 |
| ThrombocytopeniaBlood and lymphatic system disorders | 6/59 | 1/16 |
| FatigueGeneral disorders | 5/59 | 0/16 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 5/59 | 1/16 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 1/59 | 1/16 |
| Event | Methotrexate | Cyclophosphamide |
|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 49/59 | 6/16 |
| AnemiaBlood and lymphatic system disorders | 41/59 | 5/16 |
| LeukopeniaBlood and lymphatic system disorders | 37/59 | 6/16 |
| FatigueGeneral disorders | 34/59 | 0/16 |
| HyperglycemiaMetabolism and nutrition disorders | 34/59 | 3/16 |
| AST increasedMetabolism and nutrition disorders | 21/59 | 0/16 |
| ThrombocytopeniaBlood and lymphatic system disorders | 20/59 | 1/16 |
| Bilirubin IncreasedMetabolism and nutrition disorders | 15/59 | 0/16 |
| HyponatremiaMetabolism and nutrition disorders | 14/59 | 0/16 |
| NauseaGastrointestinal disorders | 14/59 | 0/16 |
| Age, Categorical(Participants) | Methotrexate |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 20 |
| >=65 years | 35 |
| Age, Continuous(years) | Methotrexate |
|---|---|
| Mean | 65.4 ± 17.8 |
| Sex: Female, Male(Participants) | Methotrexate |
|---|---|
| Female | 25 |
| Male | 30 |
| Region of Enrollment(participants) | Methotrexate |
|---|---|
| United States | 55 |
This study is terminated, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.
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Eastern Cooperative Oncology Group