LeukemiaPhase 2NCT00110058
Fludarabine and Radiation Therapy in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Phase or Accelerated Phase Chronic Myelogenous Leukemia
A Phase 2 study testing recombinant interferon alfa, therapeutic allogeneic lymphocytes and cyclosporine in people with Leukemia, run by Fred Hutchinson Cancer Center at 3 sites in United States.
Trial summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukemia
- What is being tested?
- recombinant interferon alfa, therapeutic allogeneic lymphocytes and cyclosporine
- Type of treatment
- Surgery or procedure
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2005to Jul 2006
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia, meeting 1 of the following criteria:
- Chronic phase
- Ph+ by cytogenetics or fluorescent in situ hybridization (FISH) assay
- Accelerated phase, meeting any of the following criteria:
- More than 10% but < 30% myeloblasts and promyelocytes in marrow or peripheral blood
- Any additional clonal cytogenetic abnormalities
- Increasing splenomegaly
- Extramedullary tumor
- WBC, platelet count, or hematocrit perturbations not controlled by therapy with hydroxyurea, interferon, or imatinib mesylate
- Persistent unexplained fever or bone pain
- Less than 5% blasts in the marrow at time of transplantation
- Not eligible for OR refused conventional myeloablative allogeneic stem cell transplantation
- Failed OR suboptimal response to prior imatinib mesylate, as defined by 1 of the following:
- Absence of complete hematologic response after > 3 months of treatment with imatinib mesylate
- Absence of cytogenetic response, as defined by 1 of the following:
- Absence of any cytogenetic response (< 95% Ph+ or BCR/ABL+ cells by cytogenetic or FISH analysis, respectively) after 6 months of treatment with imatinib mesylate
- Absence of major cytogenetic response (< 35% Ph+ or BCR/ABL+ cells by cytogenetic or FISH analysis, respectively) after 1 year of treatment with imatinib mesylate
- Absence of complete cytogenetic response (no Ph+ cells by cytogenetic analysis OR BCR/ABL+ cells within normal limits by FISH analysis) after 18 months of treatment with imatinib mesylate
- Hematologic evidence of disease progression
- Cytogenetic evidence of disease progression
- Increase in Ph+ cells or BCR/ABL+ cells by > 20% with at least 1 month between sequential testing
- Molecular evidence of disease progression
- More than 10-fold increase in BCR/ABL mRNA levels by quantitative polymerase chain reaction (Q-PCR) with at least 1 month between 2 sequential tests
- Experienced adverse events during treatment with imatinib mesylate that precluded further administration of the drug
- No CNS disease refractory to intrathecal chemotherapy
- HLA identical related donor available
- Phenotypically matched at HLA-A, -B, -C, DRQ1, and DBQ1
- No presence of circulating leukemic blasts by standard pathology
PATIENT CHARACTERISTICS:
Age
- Any age
Performance status
- Karnofsky 70-100% OR
- Lansky 70-100%
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- No fulminant liver failure
- No cirrhosis of the liver with evidence of portal hypertension or bridging fibrosis
- No alcoholic hepatitis
- No esophageal varices
- No history of bleeding esophageal varices
- No hepatic encephalopathy
- No uncorrectable hepatic synthetic dysfunction evidenced by prolongation of PT
- No ascites related to portal hypertension
- No bacterial or fungal liver abscess
- No biliary obstruction
- No chronic viral hepatitis AND bilirubin > 3 mg/dL
- No symptomatic biliary disease
Renal
- Renal failure allowed
Cardiovascular
- No symptomatic coronary artery disease
- Ejection fraction ≥ 35%
- No other cardiac failure requiring therapy
- No poorly controlled hypertension (blood pressure ≥ 150/90 mm Hg) on standard medication
Pulmonary
- DLCO ≥ 30%
- Total lung capacity ≥ 30%
- FEV_1 ≥ 30%
- No requirement for continuous supplementary oxygen
- No fungal pneumonia with radiological progression after treatment with amphotericin or mold-active azoles for > 1 month
Other
- Not pregnant or nursing
- Fertile patients must use effective barrier contraception during and for 12 months after completion of study treatment
- HIV negative
- No other disease that severely limits life expectancy
- No other active malignancy except localized nonmelanoma skin cancer
- No nonhematologic malignancy within the past 5 years that is currently in complete remission and has a > 20% risk of disease recurrence except for nonmelanoma skin cancer
- No systemic uncontrolled infection
- No active bacterial or fungal infection unresponsive to medical therapy
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- At least 48 hours since prior imatinib mesylate
Trial locations and contacts
3 sites in 1 country.
United States3 sites
City of Hope Comprehensive Cancer Center
Duarte, California, 91010-3000
Seattle Cancer Care Alliance
Seattle, Washington, 98109-1023
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024
About this study
Official title: A Multi-Center Phase II Study of Nonmyeloablative Conditioning With TBI and Fludarabine for HLA-Matched Related Hematopoietic Cell Transplantation for Treatment of Chronic Myeloid Leukemia in Chronic and Accelerated Phase
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy 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). Giving an infusion of the donor's T cells (donor lymphocyte infusion) or interferon alfa after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine together with radiation therapy works in treating patients who are undergoing donor stem cell transplant for chronic phase or accelerated phase chronic myelogenous leukemia.
Read the detailed description
OBJECTIVES:
Primary
- Determine the disease-free survival rate in patients with chronic or accelerated phase chronic myelogenous leukemia that failed or inadequately responded to prior imatinib mesylate treated with nonmyeloablative conditioning comprising fludarabine and low-dose total-body irradiation followed by allogeneic peripheral blood stem cell transplantation.
Secondary
- Determine the complete cytogenetic and molecular response rates in patients treated with this regimen.
- Determine overall survival of patients treated with this regimen.
- Determine non-relapse mortality in patients treated with this regimen.
- Determine the incidence of serious infection, graft-versus-host disease, and myelosuppression in patients treated with this regimen.
OUTLINE: This is a multicenter study.
- Conditioning treatment: Patients receive fludarabine IV on days -4 to -2. Patients undergo low-dose total-body irradiation (TBI) on day 0.
- Allogeneic peripheral blood stem cell transplantation: After TBI, patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
- Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease (GVHD). Patients also receive oral mycophenolate mofetil twice daily on days 0-27.
- Post-transplant treatment: Patients experiencing disease persistence or progression AND low donor chimerism discontinue immunosuppression. Patients with disease persistence or progression after discontinuing immunosuppression receive oral imatinib mesylate once daily. Patients who have disease improvement after day 28 of imatinib mesylate treatment AND who have no evidence of disease after day 84 of imatinib mesylate treatment continue imatinib mesylate in the absence of disease progression or unacceptable toxicity. Patients who fail to improve after day 28 of imatinib mesylate treatment OR who have residual disease after day 84 of imatinib mesylate treatment receive donor lymphocytes IV over 15-30 minutes once every 1-4 months for up to 4 infusions. Patients ineligible to receive donor lymphocytes (e.g., patients with evidence of GVHD) receive interferon alfa subcutaneously 3 times a week for up to 12 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 6, 9, 12, 18, and 24 months, and then annually for 5 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
- Conditions
- Leukemia
- Being tested
- recombinant interferon alfa, therapeutic allogeneic lymphocytes, cyclosporine, fludarabine phosphate, imatinib mesylate
- Keywords
- accelerated phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, Philadelphia chromosome positive chronic myelogenous leukemia, relapsing chronic myelogenous leukemia
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Accelerated Phase, Leukemia, Myeloid, Chronic-Phase, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant interferon alfaBiological
therapeutic allogeneic lymphocytesBiological
cyclosporineDrug
imatinib mesylateDrug
peripheral blood stem cell transplantationProcedure or surgery
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Secondary outcomes (6)
Rate of complete molecular response
Late nonrelapse mortality
Incidence and severity of graft-vs-host disease (GVHD)
Incidence of serious infections
Myelosuppression
Overall survival and disease-free survival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2005 (estimated)
- Study startFeb 2005
- Study completionJul 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Brenda Sandmaier, MD, Principal investigator, Fred Hutchinson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00110058
- Sponsor's protocol ID
- 1954.00
- Other IDs
- FHCRC-1954.00, CDR0000423314
- Status last verified
- Nov 2011
- First submitted
- 3 May 2005
- Last updated
- 17 Nov 2011
- Results posted
- No
Publications
Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.
PubMed 32499241
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center Phase II Study of Nonmyeloablative Conditioning With TBI and Fludarabine for HLA-Matched Related Hematopoietic Cell Transplantation for Treatment of Chronic Myeloid Leukemia in Chronic and Accelerated Phase
- ClinicalTrials.gov ID
- NCT00110058
- Acronym / sponsor ID
- 1954.00
- Conditions
- Leukemia
- Keywords
- accelerated phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, Philadelphia chromosome positive chronic myelogenous leukemia, relapsing chronic myelogenous leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2005
- Study completion
- Jul 2006 (actual)
- First posted
- 4 May 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy 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). Giving an infusion of the donor's T cells (donor lymphocyte infusion) or interferon alfa after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine together with radiation therapy works in treating patients who are undergoing donor stem cell transplant for chronic phase or accelerated phase chronic myelogenous leukemia.
Detailed description
OBJECTIVES:
Primary
- Determine the disease-free survival rate in patients with chronic or accelerated phase chronic myelogenous leukemia that failed or inadequately responded to prior imatinib mesylate treated with nonmyeloablative conditioning comprising fludarabine and low-dose total-body irradiation followed by allogeneic peripheral blood stem cell transplantation.
Secondary
- Determine the complete cytogenetic and molecular response rates in patients treated with this regimen.
- Determine overall survival of patients treated with this regimen.
- Determine non-relapse mortality in patients treated with this regimen.
- Determine the incidence of serious infection, graft-versus-host disease, and myelosuppression in patients treated with this regimen.
OUTLINE: This is a multicenter study.
- Conditioning treatment: Patients receive fludarabine IV on days -4 to -2. Patients undergo low-dose total-body irradiation (TBI) on day 0.
- Allogeneic peripheral blood stem cell transplantation: After TBI, patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
- Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease (GVHD). Patients also receive oral mycophenolate mofetil twice daily on days 0-27.
- Post-transplant treatment: Patients experiencing disease persistence or progression AND low donor chimerism discontinue immunosuppression. Patients with disease persistence or progression after discontinuing immunosuppression receive oral imatinib mesylate once daily. Patients who have disease improvement after day 28 of imatinib mesylate treatment AND who have no evidence of disease after day 84 of imatinib mesylate treatment continue imatinib mesylate in the absence of disease progression or unacceptable toxicity. Patients who fail to improve after day 28 of imatinib mesylate treatment OR who have residual disease after day 84 of imatinib mesylate treatment receive donor lymphocytes IV over 15-30 minutes once every 1-4 months for up to 4 infusions. Patients ineligible to receive donor lymphocytes (e.g., patients with evidence of GVHD) receive interferon alfa subcutaneously 3 times a week for up to 12 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 6, 9, 12, 18, and 24 months, and then annually for 5 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| recombinant interferon alfa | Biological | – |
| therapeutic allogeneic lymphocytes | Biological | – |
| cyclosporine | Drug | – |
| fludarabine phosphate | Drug | – |
| imatinib mesylate | Drug | – |
| mycophenolate mofetil | Drug | – |
| peripheral blood stem cell transplantation | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Progression-free survival
6 secondary outcomes
Rate of complete molecular response
Late nonrelapse mortality
Incidence and severity of graft-vs-host disease (GVHD)
Incidence of serious infections
Myelosuppression
Overall survival and disease-free survival
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2011.
- Derived from this study: PubMed 32499241Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brenda Sandmaier, MD principal investigator
Fred Hutchinson Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing recombinant interferon alfa, therapeutic allogeneic lymphocytes and cyclosporine in people with Leukemia, run by Fred Hutchinson Cancer Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00110058, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2011.