LeukemiaPhase 2NCT00619645
Donor Peripheral Stem Cell Transplant, Fludarabine, and Busulfan in Treating Patients With Hematologic Cancers
A Phase 2 study testing busulfan, cyclosporine and fludarabine phosphate in people with Leukemia and Lymphoma, run by University of California, Davis at 1 site in United States.
Trial summary
Giving chemotherapy drugs, such as fludarabine and busulfan, before a donor peripheral 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?
- Ages 18 to 120 years
- Conditions the study is for
- Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- busulfan, cyclosporine and fludarabine phosphate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2007to Nov 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosed with any of the following:
- Acute myeloid leukemia (AML), meeting 1 of the following criteria:
- Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
- In first complete remission (CR1) with poor-risk cytogenetics, antecedent hematological disease (i.e., myelodysplasia), or treatment-related leukemia
- Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:
- Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
- CR1 with Philadelphia chromosome or poor-risk cytogenetics
- Chronic myelogenous leukemia (CML), meeting the following criteria:
- First or second chronic phase
- Must be documented disease progression after imatinib mesylate therapy OR documented lack of cytogenetic response 6 months post-imatinib mesylate initiation OR imatinib mesylate intolerance
- Chronic lymphocytic leukemia (CLL), meeting the following criteria:
- Recurrent disease after fludarabine-based therapy
- Must have chemosensitive disease at the time of relapse, defined as greater than 50% reduction of WBC and lymphadenopathy
- Recurrent Hodgkin lymphoma, recurrent non-Hodgkin lymphoma (NHL) (low-, intermediate-, or high-grade disease*), or transformed NHL, meeting 1 of the following criteria:
- Received prior autologous transplantation and cytoreductive therapy at the time of relapse to achieve complete remission (CR) or CR/unconfirmed (CRu) as defined by the International Workshop
- Relapsed disease that required more than 2 salvage regimens to achieve CR or CRu
- Recurrent multiple myeloma, meeting the following criteria:
- Must have received prior autologous transplantation and demonstrate chemosensitivity at the time of relapse, defined as greater than 50% reduction of M-component or plasma-cell marrow infiltration
- Myelodysplastic syndrome
- Refractory anemia (RA)/RA with ringed sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD)/refractory cytopenia with multilineage dysplasia with ringed sideroblasts (RCMD-RS), or RA with excess blasts (RAEB) I, meeting the following criteria:
- Must be transfusion-dependent and have an IPSS score ≥ 1.5, based on WHO criteria
- No RAEB II or del(5q)
- No uncontrolled CNS metastases
- 5-6/6 HLA-matched sibling or 9-10/10 matched unrelated donor (both patient and donor) available
PATIENT CHARACTERISTICS:
- Karnofsky performance status ≥ 50%
- Serum creatinine ≤ 2 mg/dL
- Not pregnant
- Fertile patients must use effective contraception
- 50 years of age or older
- Patients 18-50 years of age are eligible if meeting 1 of the following criteria:
- Have a preexisting medical condition
- Received prior therapy (i.e., autologous transplantation) and are considered to be too high risk for conventional myeloablative transplantation
- Must be willing to accept or comprehend irreversible sterility as a side effect of therapy
- No uncontrolled active infection
- No psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
- Cardiac ejection fraction ≥ 30%
- Corrected pulmonary-diffusing capacity ≥ 35%
- No serologic evidence of infection with HIV
- No decompensated liver disease with serum bilirubin > 2.0 mg/dL
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis Cancer Center
Sacramento, California, 95817
About this study
Official title: Reduced Intensity Stem Cell Transplantation (RIST) for Patients With Hematological Malignancies Conditioned With Fludarabine and Busulfan
Giving chemotherapy drugs, such as fludarabine and busulfan, before a donor peripheral 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 cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying the side effects of giving donor peripheral stem cell transplant together with fludarabine and busulfan and to see how well it works in treating patients with hematologic cancers.
Read the detailed description
OUTLINE:
- Conditioning regimen: Patients receive busulfan IV over 3 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
- Allogeneic peripheral blood stem cell transplant (PBSC): Patients undergo allogeneic PBSC on day 0.
- Immunosuppressive therapy/graft-versus-host disease (GVHD) prophylaxis: Patients achieve100% donor T-cell chimerism on day 30 without disease recurrence, and cyclosporine A (CSA) IV continuously over 24 hours or orally every 12 hours on days -1 to 60 followed by a taper until day 100 and oral mycophenolate mofetil (MMF) once every 12 hours on days 1-40, in the absence of ≥ grade 2 GVHD.
Patients with recurrent disease or < 100% donor T-cell chimerism (on day 30) undergo a 12-day CSA and MMF taper followed by escalating doses of previously collected donor leukocyte infusion every 4 weeks until 100% donor T-cell chimerism or disease regression, in the absence of ≥ grade 2 GVHD.
After completion of study treatment, patients are followed periodically.
- Being tested
- busulfan, cyclosporine, fludarabine phosphate, mycophenolate mofetil, allogeneic hematopoietic stem cell transplantation
- Keywords
- recurrent adult acute myeloid leukemia, adult acute lymphoblastic leukemia in remission, refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, refractory anemia, refractory cytopenia with multilineage dysplasia, previously treated myelodysplastic syndromes, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, refractory chronic lymphocytic leukemia, recurrent adult Hodgkin lymphoma, refractory multiple myeloma, recurrent adult acute lymphoblastic leukemia, stage III chronic lymphocytic leukemia
- Medical subject headings
- Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts, Anemia, Refractory
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
busulfanDrug
cyclosporineDrug
allogeneic hematopoietic stem cell transplantationProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| RIST for Heme malignancies | Other | Busulfan 3.3 mg/kg over 3 hours on day -6 and day -5 Fludarabine 30 mg/m2 IV over 30 minutes on day -6 to day -2 followed by Transplant followed by Immunosuppressive/GVHD therapy Receives: Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Day 100 Transplant-related Mortality
Patients were followed for death and whether or not that death was attributed to the day 100 transplant via physician assessment for 24 months after day 100 transplant.
Measured: 24 months after day 100 transplant
Secondary outcomes (2)
Number of Patients Without Progression After Day 100 Transplant
All patients will be followed for progression for 24 months after their day 100 transplant.
Measured: 24 months after day 100 transplant
Number of Patients Alive 24 Months Post Day 100 Transplant
Patients will be followed for survival for 24 months post day 100 transplant.
Measured: 24 months post day 100 transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2008 (estimated)
- Study startJun 2007
- Primary completionOct 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carol M. Richman, MD, Study chair, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00619645
- Sponsor's protocol ID
- UCDCC#196
- Other IDs
- 288263, UCD-196
- Status last verified
- Jan 2018
- First submitted
- 20 Feb 2008
- Last updated
- 10 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Intensity Stem Cell Transplantation (RIST) for Patients With Hematological Malignancies Conditioned With Fludarabine and Busulfan
- ClinicalTrials.gov ID
- NCT00619645
- Acronym / sponsor ID
- UCDCC#196
- Keywords
- recurrent adult acute myeloid leukemia, adult acute lymphoblastic leukemia in remission, refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, refractory anemia, refractory cytopenia with multilineage dysplasia, previously treated myelodysplastic syndromes, adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- Oct 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 21 Feb 2008 (estimated)
- Results
- Posted 8 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Giving chemotherapy drugs, such as fludarabine and busulfan, before a donor peripheral 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 cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying the side effects of giving donor peripheral stem cell transplant together with fludarabine and busulfan and to see how well it works in treating patients with hematologic cancers.
Detailed description
OUTLINE:
- Conditioning regimen: Patients receive busulfan IV over 3 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
- Allogeneic peripheral blood stem cell transplant (PBSC): Patients undergo allogeneic PBSC on day 0.
- Immunosuppressive therapy/graft-versus-host disease (GVHD) prophylaxis: Patients achieve100% donor T-cell chimerism on day 30 without disease recurrence, and cyclosporine A (CSA) IV continuously over 24 hours or orally every 12 hours on days -1 to 60 followed by a taper until day 100 and oral mycophenolate mofetil (MMF) once every 12 hours on days 1-40, in the absence of ≥ grade 2 GVHD.
Patients with recurrent disease or < 100% donor T-cell chimerism (on day 30) undergo a 12-day CSA and MMF taper followed by escalating doses of previously collected donor leukocyte infusion every 4 weeks until 100% donor T-cell chimerism or disease regression, in the absence of ≥ grade 2 GVHD.
After completion of study treatment, patients are followed periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RIST for Heme malignancies | Other | Drug: busulfan, Drug: cyclosporine, Drug: fludarabine phosphate, Drug: mycophenolate mofetil, Procedure: allogeneic hematopoietic stem cell transplantation, Procedure: peripheral blood stem cell transplantationBusulfan 3.3 mg/kg over 3 hours on day -6 and day -5 Fludarabine 30 mg/m2 IV over 30 minutes on day -6 to day -2 followed by Transplant followed by Immunosuppressive/GVHD therapy |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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 |
|---|---|---|
| busulfan | Drug | RIST for Heme malignancies |
| cyclosporine | Drug | RIST for Heme malignancies |
| fludarabine phosphate | Drug | RIST for Heme malignancies |
| mycophenolate mofetil | Drug | RIST for Heme malignancies |
| allogeneic hematopoietic stem cell transplantation | Procedure or surgery | RIST for Heme malignancies |
| peripheral blood stem cell transplantation | Procedure or surgery | RIST for Heme malignancies |
Primary outcome
Number of Patients With Day 100 Transplant-related Mortality
Time frame: 24 months after day 100 transplant
Patients were followed for death and whether or not that death was attributed to the day 100 transplant via physician assessment for 24 months after day 100 transplant.
2 secondary outcomes
Number of Patients Without Progression After Day 100 Transplant
Time frame: 24 months after day 100 transplant
Number of Patients Alive 24 Months Post Day 100 Transplant
Time frame: 24 months post day 100 transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Carol M. Richman, MD study chair
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing busulfan, cyclosporine and fludarabine phosphate in people with Leukemia and Lymphoma, run by University of California, Davis at 1 site in United States.
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 10 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 8 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients With Day 100 Transplant-related Mortality (time frame: 24 months after day 100 transplant). It is what the study was designed to measure, not a finding.
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 10 Jan 2018.