LeukemiaPhase 1/2NCT00027547
Combination Chemotherapy and Total-Body Irradiation Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia
A Phase 1/2 study testing therapeutic allogeneic lymphocytes, cyclosporine and cytarabine in people with Leukemia, run by Fred Hutchinson Cancer Center at 3 sites in 2 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Leukemia
- What is being tested?
- therapeutic allogeneic lymphocytes, cyclosporine and cytarabine
- Type of treatment
- Surgery or procedure
- How many people
- Not given
- Where
- 3 sitesin 2 countries
- Study dates
- Jul 2001to Jul 2004
- Phase
- Phase 1/2
- 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 Up to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of acute lymphoblastic leukemia (ALL)
- Adult patients must meet 1 of the following criteria:
- Age 50 to 75 with high-risk ALL in complete remission (CR) (less than 5% blasts by morphology on bone marrow aspirate and absence of peripheral blasts) or ALL in second CR (CR2) or greater
- Age 18 to 50 with high-risk ALL in first CR (CR1) and either ineligible for conventional allogeneic transplantation (based on general medical condition) or refused conventional transplantation
- High-risk adult ALL in CR1 includes patients meeting 1 or more of the following criteria:
- Age 30 and over
- Non-T-cell phenotype
- Cytogenetic abnormalities including t(9;22), t(4;11), trisomy 8, or monosomy 7
- Failure to achieve CR after 4 weeks of induction chemotherapy
- Age 18 to 50 with ALL in CR2 or greater and ineligible for conventional allogeneic transplantation based on general medical condition
- Age 18 to 50 with high-risk ALL in CR2 or greater and refused conventional allogeneic transplantation
- Pediatric patients must meet 1 of the following criteria:
- Under age 18 with high-risk ALL in CR1 and ineligible for conventional allogeneic transplantation based on general medical condition
- High-risk pediatric ALL in CR1 includes patients meeting 1 or more of the following criteria:
- Cytogenetic abnormalities
- t(9;22) with WBC at least 25,000/mm3 at diagnosis
- t(4;11) in patients under age 1 or age 10 and over
- Hypodiploidy (no more than 45 chromosomes)
- Failure to achieve CR after 4 weeks of induction chemotherapy
- Persistent peripheral blasts after 1 week of induction chemotherapy
- Under age 18 with CR2 or greater and ineligible for conventional allogeneic transplantation based on general medical condition
- Age 12 and under allowed if approved by the principle investigator
- No active CNS disease
- Availability of a sibling donor (excluding an identical twin)
- HLA genotypically identical for at least 1 haplotype
- HLA-A, -B, -C, -DRB1, and -DQB1 genotypically or phenotypically identical
PATIENT CHARACTERISTICS:
Age:
- See Disease Characteristics
- 75 and under
Performance status:
- Karnofsky 50-100% (adults)
- Lansky 40-100% (children)
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
Hepatic:
- No fulminant liver failure
- No alcoholic hepatitis
- No history of bleeding esophageal varices
- No grade II or greater hepatic encephalopathy
- No hepatic synthetic dysfunction evidenced by prolongation of PT with INR greater than 2.5
- No intractable ascites related to portal hypertension
- No bacterial or fungal liver abscess
- No chronic viral hepatitis with bilirubin greater than 5 mg/dL
- No biliary obstruction with bilirubin greater than 5 mg/dL
- No concurrent symptomatic biliary disease
Renal:
- Not specified
Cardiovascular:
- Cardiac ejection fraction at least 30%
Pulmonary:
- No requirement for supplementary continuous oxygen
Other:
- HIV negative
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 1 year after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent posttransplantation growth factors during mycophenolate mofetil administration
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Cancer Institute at Oregon Health and Science University
Portland, Oregon, 97239
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024
About this study
Official title: Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Mycophenolate mofetil and donor white blood cells may prevent this from happening.
PURPOSE: Phase I/II trial to determine the effectiveness of combination chemotherapy and total-body irradiation followed by peripheral stem cell transplantation in treating patients who have acute lymphoblastic leukemia.
Read the detailed description
OBJECTIVES:
- Determine if a one-year disease free survival of 40% and a day 200 transplant-related mortality of less than 25% can be achieved in patients with high-risk acute lymphoblastic leukemia in complete remission treated with a nonmyeloablative conditioning regimen comprising fludarabine and total body irradiation followed by allogeneic peripheral blood stem cell or bone marrow transplantation.
- Evaluate the efficacy and toxicity of donor lymphocyte infusion in the treatment of minimal residual disease after nonmyeloablative allografting in these patients.
OUTLINE: This is a multicenter study.
Patients receive a nonmyeloablative conditioning regimen comprising fludarabine IV on days -4 to -2 and total body irradiation (TBI) on day 0. Children undergo allogeneic peripheral blood stem cell transplantation (PBSCT) or bone marrow transplantation after TBI on day 0. Adults undergo filgrastim (G-CSF)-mobilized allogeneic PBSCT after TBI on day 0.
Patients also receive graft-versus-host disease (GVHD) prophylaxis therapy comprising oral cyclosporine twice daily on days -3 to 56 and then tapered and oral mycophenolate mofetil once at 5-10 hours after transplantation on day 0 and then twice daily on days 1-27.
Patients who have no evidence of grade 2 or greater acute GVHD or clinically extensive chronic GVHD, have been off GVHD prophylaxis therapy for 1-2 weeks, and have stable or increasing minimal residual disease after discontinuation of GVHD prophylaxis therapy receive donor lymphocyte infusion (DLI) IV over 30 minutes. DLI repeats every 4 weeks for a total of 3 doses (if necessary).
Patients without a history of CNS leukemia and patients with a history of CNS leukemia previously treated with prophylactic craniospinal irradiation receive methotrexate (MTX) or cytarabine (ARA-C) intrathecally (IT) for a total of 2 doses before transplantation and for a total of 6 doses beginning on day 32 after transplantation. Patients with a history of CNS leukemia not previously treated with craniospinal irradiation undergo craniospinal irradiation for 11 days before conditioning regimen and then MTX or ARA-C IT for a total of 6 doses beginning on day 32 after transplantation. Male patients also undergo testicular radiotherapy for 7 days.
Patients are followed at 1, 2, 3, 6, 12, 18, and 24 months.
PROJECTED ACCRUAL: A total of 30 patients (20 adults and 10 children) will be accrued for this study within 2 years.
- Conditions
- Leukemia
- Being tested
- therapeutic allogeneic lymphocytes, cyclosporine, cytarabine, fludarabine phosphate, methotrexate
- Keywords
- adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic allogeneic lymphocytesBiological
cyclosporineDrug
cytarabineDrug
methotrexateDrug
allogeneic bone marrow transplantationProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
radiation therapyRadiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startJul 2001
- Study completionJul 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Masking
- None (open label)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- George Georges, MD, Study chair, Fred Hutchinson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00027547
- Sponsor's protocol ID
- 1586.00
- Other IDs
- FHCRC-1586.00, NCI-H01-0080, CDR0000069042
- Status last verified
- Nov 2011
- First submitted
- 7 Dec 2001
- Last updated
- 30 Nov 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission
- ClinicalTrials.gov ID
- NCT00027547
- Acronym / sponsor ID
- 1586.00
- Conditions
- Leukemia
- Keywords
- adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2001
- Study completion
- Jul 2004 (actual)
- First posted
- 27 Jan 2003 (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: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Mycophenolate mofetil and donor white blood cells may prevent this from happening.
PURPOSE: Phase I/II trial to determine the effectiveness of combination chemotherapy and total-body irradiation followed by peripheral stem cell transplantation in treating patients who have acute lymphoblastic leukemia.
Detailed description
OBJECTIVES:
- Determine if a one-year disease free survival of 40% and a day 200 transplant-related mortality of less than 25% can be achieved in patients with high-risk acute lymphoblastic leukemia in complete remission treated with a nonmyeloablative conditioning regimen comprising fludarabine and total body irradiation followed by allogeneic peripheral blood stem cell or bone marrow transplantation.
- Evaluate the efficacy and toxicity of donor lymphocyte infusion in the treatment of minimal residual disease after nonmyeloablative allografting in these patients.
OUTLINE: This is a multicenter study.
Patients receive a nonmyeloablative conditioning regimen comprising fludarabine IV on days -4 to -2 and total body irradiation (TBI) on day 0. Children undergo allogeneic peripheral blood stem cell transplantation (PBSCT) or bone marrow transplantation after TBI on day 0. Adults undergo filgrastim (G-CSF)-mobilized allogeneic PBSCT after TBI on day 0.
Patients also receive graft-versus-host disease (GVHD) prophylaxis therapy comprising oral cyclosporine twice daily on days -3 to 56 and then tapered and oral mycophenolate mofetil once at 5-10 hours after transplantation on day 0 and then twice daily on days 1-27.
Patients who have no evidence of grade 2 or greater acute GVHD or clinically extensive chronic GVHD, have been off GVHD prophylaxis therapy for 1-2 weeks, and have stable or increasing minimal residual disease after discontinuation of GVHD prophylaxis therapy receive donor lymphocyte infusion (DLI) IV over 30 minutes. DLI repeats every 4 weeks for a total of 3 doses (if necessary).
Patients without a history of CNS leukemia and patients with a history of CNS leukemia previously treated with prophylactic craniospinal irradiation receive methotrexate (MTX) or cytarabine (ARA-C) intrathecally (IT) for a total of 2 doses before transplantation and for a total of 6 doses beginning on day 32 after transplantation. Patients with a history of CNS leukemia not previously treated with craniospinal irradiation undergo craniospinal irradiation for 11 days before conditioning regimen and then MTX or ARA-C IT for a total of 6 doses beginning on day 32 after transplantation. Male patients also undergo testicular radiotherapy for 7 days.
Patients are followed at 1, 2, 3, 6, 12, 18, and 24 months.
PROJECTED ACCRUAL: A total of 30 patients (20 adults and 10 children) will be accrued for this study within 2 years.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 75 years
- 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 |
|---|---|---|
| therapeutic allogeneic lymphocytes | Biological | – |
| cyclosporine | Drug | – |
| cytarabine | Drug | – |
| fludarabine phosphate | Drug | – |
| methotrexate | Drug | – |
| mycophenolate mofetil | Drug | – |
| allogeneic bone marrow transplantation | Procedure or surgery | – |
| peripheral blood stem cell transplantation | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Not reported in the source record.
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 30 Nov 2011.
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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.
George Georges, MD study chair
Fred Hutchinson Cancer Center
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing therapeutic allogeneic lymphocytes, cyclosporine and cytarabine in people with Leukemia, run by Fred Hutchinson Cancer Center at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 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, Germany. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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.
Where can I read the original study information?
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 30 Nov 2011.