A Phase 2 interventional study of fludarabine phosphate and total-body irradiation in Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission and Adult Acute Myeloid Leukemia in Remission, sponsored by Fred Hutchinson Cancer Center. Completed at 5 sites in 2 countries. Open to participants aged Up to 74 Years. Per ClinicalTrials.gov, last updated 2020-01-29.
Sponsored by Fred Hutchinson Cancer Center · Phase 2, Interventional, and Treatment
This phase II trial studies how well tacrolimus and mycophenolate mofetil works in preventing graft-versus-host disease in patients who have undergone total-body irradiation (TBI) with or without fludarabine phosphate followed by donor peripheral blood stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI 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 system 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 and mycophenolate mofetil after the transplant may stop this from happening.
PRIMARY OBJECTIVES:
I. To estimate the incidence of grade III/IV graft-versus-host disease (GVHD) after conditioning with 200 centigray (cGy) TBI alone or Fludarabine (fludarabine phosphate)/200 cGy TBI followed by tacrolimus (Tac)/mycophenolate mofetil (MMF) immunosuppression in patients with hematologic malignancies.
II. To estimate the incidence of chronic extensive GVHD.
SECONDARY OBJECTIVES:
I. To estimate the incidences of graft rejection.
II. To estimate overall survival 1-year after conditioning.
III. To evaluate the incidences of grades II-IV acute GVHD.
IV. To evaluate the rates of disease progression and/or relapse-related mortality.
V. To estimate the rate and duration of steroid use for the treatment of chronic GVHD.
OUTLINE: Patients are assigned to 1 of 2 treatment arms.
ARM I (nonmyeloablative conditioning with fludarabine phosphate and TBI): Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0.
ARM II (nonmyeloablative conditioning with TBI): Patients undergo TBI on day 0.
All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus orally (PO) every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.
270 studies on the registry are indexed under Lymphoma, Extranodal NK-T-Cell; 36 are open to participants now.
This study's enrollment of 150 is above the median of 33 across 225 interventional studies indexed under Lymphoma, Extranodal NK-T-Cell.
Browse Lymphoma, Extranodal NK-T-Cell studies →Fred Hutchinson Cancer Center is the lead sponsor of 547 studies on the registry; 80 are open to participants now.
Of its 59 completed or terminated interventional studies of FDA-regulated products, 46 (78%) have results posted.
Compared within Lymphoma, Extranodal NK-T-Cell, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Leukemia, Myeloid, Accelerated Phase. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.
Drug: fludarabine phosphate · Radiation: total-body irradiation · Other: laboratory biomarker analysis
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO.
Radiation: total-body irradiation · Drug: mycophenolate mofetil · Drug: tacrolimus · Procedure: peripheral blood stem cell transplantation · Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation · Other: laboratory biomarker analysis
Given IV
Also known as: 2-F-ara-AMP, Beneflur, Fludara
Undergo radiotherapy
Also known as: TBI
Given IV or PO
Also known as: Cellcept, MMF
Given IV or PO
Also known as: FK 506, Prograf
Undergo allogeneic peripheral blood stem cell transplant
Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Undergo allogeneic peripheral blood stem cell transplant
Correlative studies
Incidence of Grade III/IV GVHD
Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
Time frame: Day 180 post-transplantation
Incidence of Chronic Extensive GVHD
Number of patients who developed chronic extensive GVHD post-transplant. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
Time frame: Day 180 post-transplantation
Incidences of Graft Rejection
Number of patients who rejected their graft. Rejection is defined as the inability to detect or loss of detection of greater than 5% donor T cells (CD3+) as a proportion of the total T cell population, respectively, after nonmyeloablative HCT.
Time frame: Day 180 post-transplantation
Overall Survival
Number of patients surviving post-transplant.
Time frame: At 1 year after conditioning
Incidences of Grades II-IV Acute GVHD
Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
Time frame: Day 180 post-transplantation
Rates of Disease Progression
Relapse/Progression criteria: CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever \>38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes \>20%. CMML, AML, ALL \>30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia. CLL ≥1 of: Physical exam/imaging studies ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL \>25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.
Time frame: Up to 5 years
Rates of Relapse-related Mortality
Number of patients who expired with relapsed/progressive disease.
Time frame: Up to 5 years
Rate and Duration of Steroid Use for the Treatment of Chronic GVHD
Number of patients that received prednisone treatment of chronic GVHD, and number of days for which they received prednisone.
Time frame: Up to 5 years
| Milestone | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Started | 100 | 50 |
| Completed | 100 | 50 |
| Not completed | 0 | 0 |
Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
| Participants | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Incidence of Grade III/IV GVHD | 2 | 4 |
Number of patients who developed chronic extensive GVHD post-transplant. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
| Participants | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Incidence of Chronic Extensive GVHD | 15 | 6 |
Number of patients who rejected their graft. Rejection is defined as the inability to detect or loss of detection of greater than 5% donor T cells (CD3+) as a proportion of the total T cell population, respectively, after nonmyeloablative HCT.
| Participants | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Incidences of Graft Rejection | 0 | 0 |
Number of patients surviving post-transplant.
| Participants | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Overall Survival | 85 | 39 |
Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
| Participants | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Incidences of Grades II-IV Acute GVHD | 26 | 14 |
Relapse/Progression criteria: CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever \>38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes \>20%. CMML, AML, ALL \>30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia. CLL ≥1 of: Physical exam/imaging studies ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL \>25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.
| Participants | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Rates of Disease Progression | 41 | 33 |
Number of patients who expired with relapsed/progressive disease.
| Participants | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Rates of Relapse-related Mortality | 28 | 23 |
Number of patients that received prednisone treatment of chronic GVHD, and number of days for which they received prednisone.
| days | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Rate and Duration of Steroid Use for the Treatment of Chronic GVHD | 78 (1 to 1156) | 89 (1 to 420) |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | — | 8/100 (8%) | 28/100 (28%) |
| Arm II (Nonmyeloablative Conditioning With TBI) | — | 5/50 (10%) | 17/50 (34%) |
| Event | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Hypoxia and HypotensionVascular disorders | 0/100 | 1/50 |
| Death, secondary to sepsis with multiorgan failureInfections and infestations | 0/100 | 1/50 |
| Perforated gastric ulcerGastrointestinal disorders | 0/100 | 1/50 |
| Death due to adenovirus nephritis, sepsis, multifactorial renal failureInfections and infestations | 0/100 | 1/50 |
| Elevated creatinine levelRenal and urinary disorders | 0/100 | 1/50 |
| Death, Renal Failure, Cardiac FailureCardiac disorders | 1/100 | 0/50 |
| Death due to severe refractory autoimmune hemolytic anemia (present prior to transplant)Immune system disorders | 1/100 | 0/50 |
| Death, elevated bilirubin, feversHepatobiliary disorders | 1/100 | 0/50 |
| Right central artery occlusion with right eye blindnessEye disorders | 1/100 | 0/50 |
| Severe abdominal pain due to gut GVHD and supravantricular arrhythmia/Atrial fibrillationImmune system disorders | 1/100 | 0/50 |
| Event | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) |
|---|---|---|
| Increased CreatinineRenal and urinary disorders | 20/100 | 15/50 |
| HyperbilirubinemiaHepatobiliary disorders | 8/100 | 3/50 |
| HypotensionCardiac disorders | 1/100 | 4/50 |
| Hemolysis / Hemolytic AnemiaBlood and lymphatic system disorders | 5/100 | 1/50 |
| Hypoxia / HypoxemiaRespiratory, thoracic and mediastinal disorders | 5/100 | 2/50 |
| Age, Categorical(Participants) | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 74 | 49 | 123 |
| >=65 years | 26 | 1 | 27 |
| Sex: Female, Male(Participants) | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) | Total |
|---|---|---|---|
| Female | 46 | 17 | 63 |
| Male | 54 | 33 | 87 |
| Region of Enrollment(participants) | Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI) | Arm II (Nonmyeloablative Conditioning With TBI) | Total |
|---|---|---|---|
| United States | 98 | 46 | 144 |
| Italy | 2 | 4 | 6 |
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Studies of the drugs tested here: Fludarabine phosphate · Mycophenolic Acid · Tacrolimus
Lymphoma, Extranodal NK-T-Cell →
Fred Hutchinson Cancer Center →