A Phase 2 interventional study of anti-thymocyte globulin and cyclophosphamide in Chronic Myeloproliferative Disorders, Graft Versus Host Disease and Infection, sponsored by City of Hope Medical Center. Completed at 2 sites in United States. Open to participants aged 2 Years and older. Per ClinicalTrials.gov, last updated 2014-09-10.
Sponsored by City of Hope Medical Center · Phase 2, Interventional, and Supportive care
RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients are stratified according to conditioning regimen (fludarabine phosphate and melphalan vs fractionated total-body irradiation [FTBI] and etoposide vs FTBI and cyclophosphamide) and degree of donor/recipient HLA mismatch (high-risk vs low-risk).
NOTE: *Only patients with high-risk HLA mismatch receive treatment with methotrexate.
After completion of study therapy, patients are followed periodically for up to 2 years.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 32 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →City of Hope Medical Center is the lead sponsor of 670 studies on the registry; 181 are open to participants now.
Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Diagnosis of hematological malignancy including any of the following:
Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in any CR
Myelofibrosis and other myeloproliferative disorders
Must be planning to receive 1 of the following conditioning regimens at City of Hope:
Suitable unrelated donor available
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis
Biological: anti-thymocyte globulin · Drug: fludarabine phosphate · Drug: melphalan · Drug: methotrexate · Drug: sirolimus · Drug: tacrolimus · Procedure: allogeneic hematopoietic stem cell transplantation · Procedure: hematopoietic stem cell transplantation · Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation · Procedure: peripheral blood stem cell transplantation · Radiation: total-body irradiation
FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis
Biological: anti-thymocyte globulin · Drug: cyclophosphamide · Drug: methotrexate · Drug: sirolimus · Drug: tacrolimus · Procedure: allogeneic hematopoietic stem cell transplantation · Procedure: hematopoietic stem cell transplantation · Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation · Procedure: peripheral blood stem cell transplantation · Radiation: total-body irradiation
FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis
Biological: anti-thymocyte globulin · Drug: etoposide · Drug: methotrexate · Drug: sirolimus · Drug: tacrolimus · Procedure: allogeneic hematopoietic stem cell transplantation · Procedure: hematopoietic stem cell transplantation · Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation · Procedure: peripheral blood stem cell transplantation · Radiation: total-body irradiation
0.5 mg/kg on day -3, 1.5 mg/kg on day -2 and 2.5 mg/kg on day -1 or day 0 from stem cell transplant
60mg/kg on days -5 and -4 from stem cell transplant
60mg/kg on day -4 from stem cell transplant
Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant
Melphalan 140 mg/m2 on day -4 from stem cell transplant
For high risk HLA-mismatch transplant only: 5 mg/m2 on days +1, +3 and +6 from stem cell transplant
Adults: 12 mg loading dose on day -3 from stem cell transplant followed by 4 mg orally single morning daily dose. Pediatric Patients \<40kg: 3 mg/m2 orally on day -3 from stem cell transplant followed by 1 mg/m2 orally single morning daily dose
0.02 mg/kd/d CIV beginning on day -3 from stem cell transplant
The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight
The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight
Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant, Melphalan 140 mg/m2 on day -4 from stem cell transplant
The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight
1320 cGy in 11 fractions from day -8 to day -5 or day -9 to day -6 prior to stem cell transplant
Cumulative Incidence of Grade II-IV Acute Graft-Versus-Host Disease (GVHD) at Day 100
Patients were evaluated for the development of acute GVHD within the first 100 days post HSCT. The cumulative incidence of grade II-IV acute GVHD was determined using competing risk analysis. Competing risks for acute GVHD were death and nonengraftment.
Time frame: 100 Days Post Hematopoietic Stem Cell Transplant (HSCT)
Severity of Acute GVHD
All patients were considered for the evaluation of the severity of acute GVHD.
Time frame: 100 Days Post HSCT
Cumulative Incidence of Chronic GVHD
Patients were evaluated for the development of chronic GVHD from 101 days post HSCT to last contact or documented evidence of the disease. The cumulative incidence of chronic GVHD was determined using competing risk analysis. Competing risks for GVHD were death and nonengraftment.
Time frame: 2 year point estimate was provided.
Severity of Chronic GVHD
All Patients were considered for the evaluation of chronic GVHD severity.
Time frame: Patients were evaluated until they developed chronic GVHD, a median of 130 days post HSCT
Time to Absolute Neutrophil Count Recovery (Engraftment)
Absolute neutrophil count (ANC) recovery is defined as an ANC of ≥ 0.5 x 10\^9/L (500/mm3) for three consecutive laboratory values obtained on different days
Time frame: Patients were evaluated until neutrophil recovery, a median of 15 days post HSCT
Time to Platelet Count Recovery (Engraftment)
Platelet recovery is defined as the first date of three consecutive laboratory values ≥ 25 x 10\^9 L obtained on different days.
Time frame: Patients were evaluated until platelet recovery, a median of 14 days
Occurence of Infections Including Cytomegalovirus and Epstein-Barr Virus Reactivation
Participants were monitored throughout the trial (median of 28 months) for various infections/complications.
Time frame: Median Follow Up: 28 months (Range: 1-49 months)
Occurrence of Thrombotic Microangiopathy
Participants were monitored throughout the trial (median of 28 months) for various infections/complications. This is the number of participants who developed TMA.
Time frame: Median Follow Up: 28 Months (Range: 1-49 months)
Occurence of Sinusoidal Obstructive Syndrome (SOS)
Participants were monitored throughout the trial (median of 28 months) for various infections/complications. This is the number of participants who developed SOS.
Time frame: Median Follow Up: 28 Months (Range: 1-49 Months)
Non-relapse Mortality at 100 Days Post HSCT
Patients were evaluated for non-relapse mortality (NRM) throughout the study. Non-relapse mortality was considered any death not attributable to relapse or disease progression. The cumulative incidence of NRM was determined using competing risk analysis. Competing risks for NRM were death due to disease progression, relapse and nonengraftment.
Time frame: 100 day point estimate was provided
Non-relapse Mortality at Two Years Post HSCT
Patients were evaluated for non-relapse mortality (NRM) throughout the study. Non-relapse mortality was considered any death not attributable to relapse or disease progression. The cumulative incidence of NRM was determined using competing risk analysis. Competing risks for NRM were death due to disease progression, relapse and nonengraftment.
Time frame: 2 year point estimate was provided.
Overall Survival at Two Years Post HSCT
Patients were evaluated for survival (OS) throughout the study. Kaplan Meier estiamtes were calculated for overall survival using time from HSCT to death of any cause or for surviving patients last contact date.
Time frame: 2 year point estimate was provided.
Event Free Survival at Two Years Post HSCT
Patients were evaluated for event free survival (EFS) throughout the study. Events were defined as death, relapse, progression, or nonengraftment. Kaplan Meier estimates were calculated as time from HSCT to event.
Time frame: 2 year point estimate was provided.
Incidence of Disease Relapse/Progression at 2 Years Post HSCT
Patients were evaluated for relapse/progression post transplant throughout the study. The cumulative incidence of relapse/progression was determined using competing risk analysis. Competing risks for relapse were non-relapse mortality and nonengraftment.
Time frame: 2 year point estimate was provided.
| Milestone | All Patients |
|---|---|
| Started | 32 |
| Completed | 32 |
| Not completed | 0 |
Patients were evaluated for the development of acute GVHD within the first 100 days post HSCT. The cumulative incidence of grade II-IV acute GVHD was determined using competing risk analysis. Competing risks for acute GVHD were death and nonengraftment.
| Percentage of patients developing aGVHD | All Patients |
|---|---|
| Cumulative Incidence of Grade II-IV Acute Graft-Versus-Host Disease (GVHD) at Day 100 | 37.3 (22.4 to 62.0) |
All patients were considered for the evaluation of the severity of acute GVHD.
| participants | All Patients |
|---|---|
| No Acute GVHD | 9 |
| Yes - Grade I | 9 |
| Yes- Grade II | 9 |
| Yes- Grade III | 1 |
| Yes - Grade IV | 0 |
| No- Inevaluable (graft failures) | 4 |
Absolute neutrophil count (ANC) recovery is defined as an ANC of ≥ 0.5 x 10\^9/L (500/mm3) for three consecutive laboratory values obtained on different days
| Days | All Patients |
|---|---|
| Time to Absolute Neutrophil Count Recovery (Engraftment) | 14.5 (10 to 26) |
Platelet recovery is defined as the first date of three consecutive laboratory values ≥ 25 x 10\^9 L obtained on different days.
| Days | All Patients |
|---|---|
| Time to Platelet Count Recovery (Engraftment) | 14 (10 to 40) |
Participants were monitored throughout the trial (median of 28 months) for various infections/complications.
| participants | All Patients |
|---|---|
| Neither CMV or EBV | 16 |
| CMV reactivation only | 9 |
| EBV only | 3 |
| Both CMV and EBV | 4 |
Participants were monitored throughout the trial (median of 28 months) for various infections/complications. This is the number of participants who developed TMA.
| participants | All Patients |
|---|---|
| Occurrence of Thrombotic Microangiopathy | 7 |
Participants were monitored throughout the trial (median of 28 months) for various infections/complications. This is the number of participants who developed SOS.
| participants | All Patients |
|---|---|
| Occurence of Sinusoidal Obstructive Syndrome (SOS) | 1 |
Patients were evaluated for non-relapse mortality (NRM) throughout the study. Non-relapse mortality was considered any death not attributable to relapse or disease progression. The cumulative incidence of NRM was determined using competing risk analysis. Competing risks for NRM were death due to disease progression, relapse and nonengraftment.
| Percentage of patients with a NRM | All Patients |
|---|---|
| Non-relapse Mortality at 100 Days Post HSCT | 9.4 (3.2 to 27.5) |
Patients were evaluated for non-relapse mortality (NRM) throughout the study. Non-relapse mortality was considered any death not attributable to relapse or disease progression. The cumulative incidence of NRM was determined using competing risk analysis. Competing risks for NRM were death due to disease progression, relapse and nonengraftment.
| Percentage of patients with a NRM | All Patients |
|---|---|
| Non-relapse Mortality at Two Years Post HSCT | 15.6 (7.0 to 35.0) |
Patients were evaluated for survival (OS) throughout the study. Kaplan Meier estiamtes were calculated for overall survival using time from HSCT to death of any cause or for surviving patients last contact date.
| Percentage of patients who died | All Patients |
|---|---|
| Overall Survival at Two Years Post HSCT | 65.6 (53.7 to 75.2) |
Patients were evaluated for event free survival (EFS) throughout the study. Events were defined as death, relapse, progression, or nonengraftment. Kaplan Meier estimates were calculated as time from HSCT to event.
| Percentage of patients with an event | All Patients |
|---|---|
| Event Free Survival at Two Years Post HSCT | 61.3 (49.9 to 70.8) |
Patients were evaluated for the development of chronic GVHD from 101 days post HSCT to last contact or documented evidence of the disease. The cumulative incidence of chronic GVHD was determined using competing risk analysis. Competing risks for GVHD were death and nonengraftment.
| Percentage of patients developing cGVHD | All Patients |
|---|---|
| Cumulative Incidence of Chronic GVHD | 62.5 (47.8 to 81.7) |
All Patients were considered for the evaluation of chronic GVHD severity.
| participants | All Patients |
|---|---|
| No Chronic GVHD | 4 |
| Yes- Limited | 4 |
| Yes - Extensive | 17 |
| No- Inevaluable (graft failure/died <day 100) | 7 |
Patients were evaluated for relapse/progression post transplant throughout the study. The cumulative incidence of relapse/progression was determined using competing risk analysis. Competing risks for relapse were non-relapse mortality and nonengraftment.
| Percentage of patients who relapsed | All Patients |
|---|---|
| Incidence of Disease Relapse/Progression at 2 Years Post HSCT | 12.5 (5.0 to 31.3) |
Collected over 180 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| All Patients | — | 9/31 (29%) | 31/31 (100%) |
| Event | All Patients |
|---|---|
| DiarrheaGastrointestinal disorders | 2/31 |
| Multi-organ failureGeneral disorders | 2/31 |
| Opportunistic infectionInfections and infestations | 2/31 |
| SepsisInfections and infestations | 2/31 |
| Renal failureRenal and urinary disorders | 2/31 |
| Blood disorderBlood and lymphatic system disorders | 1/31 |
| Atrial flutterCardiac disorders | 1/31 |
| Myocardial ischemiaCardiac disorders | 1/31 |
| Ill-defined disorderGeneral disorders | 1/31 |
| PainGeneral disorders | 1/31 |
| Event | All Patients |
|---|---|
| Hemoglobin decreasedBlood and lymphatic system disorders | 31/31 |
| Leukocyte count decreasedInvestigations | 31/31 |
| Neutrophil count decreasedInvestigations | 31/31 |
| Platelet count decreasedInvestigations | 31/31 |
| Blood glucose increasedMetabolism and nutrition disorders | 31/31 |
| Serum calcium decreasedMetabolism and nutrition disorders | 31/31 |
| Serum magnesium decreasedMetabolism and nutrition disorders | 31/31 |
| Serum sodium decreasedMetabolism and nutrition disorders | 31/31 |
| FatigueGeneral disorders | 30/31 |
| Aspartate aminotransferase increasedInvestigations | 30/31 |
| Age, Continuous(years) | All Patients |
|---|---|
| Median | 59.5 (19 to 71) |
| Sex: Female, Male(Participants) | All Patients |
|---|---|
| Female | 19 |
| Male | 13 |
| Region of Enrollment(participants) | All Patients |
|---|---|
| United States | 32 |
| Diagnosis(participants) | All Patients |
|---|---|
| Acute Myeloid Leukemia | 14 |
| Myelodysplastic Syndrome | 6 |
| Acute Lymphoblastic Leukemia | 3 |
| Chronic Myeloid Leukemia | 3 |
| Non-Hodgkin Lymphoma | 3 |
| Myeloproliferative Disorder | 2 |
| Chronic Lymphocytic Leukemia | 1 |
| Disease Status (American Society for Blood and Marrow Transplantation Guidelines)(participants) | All Patients |
|---|---|
| Standard Risk | 14 |
| High/Intermediate Risk | 18 |
| Patient/Donor Cytomegalovirus (CMV) infection status(participants) | All Patients |
|---|---|
| Positive/Negative | 12 |
| Positive/Positive | 12 |
| Negative/Negative | 3 |
| Negative/Positive | 5 |
| Human Leukocyte Antigen (HLA) Match Type(participants) | All Patients |
|---|---|
| 10/10 Matched | 18 |
| 1 Mismatch | 12 |
| 2 Mismatches | 1 |
| 3 Mismatches | 1 |
| Conditioning Regimen(participants) | All Patients |
|---|---|
| Fludarabine/Melphalan | 23 |
| Fractionated Total Body Irradiation/Cytoxan | 4 |
| Fractionated Total Body Irradiation/Etoposide | 5 |
1 further baseline measures are reported on the registry.
This study is completed, as verified in Sep 2014. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
City of Hope Medical Center