LeukemiaPhase 1NCT00301951
Low-Dose Fludarabine, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer
A Phase 1 study testing anti-thymocyte globulin, sargramostim and busulfan in people with Leukemia and Lymphoma, run by University of California, San Francisco at 1 site in United States.
Trial summary
RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant helps stop both the growth of cancer cells and the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- anti-thymocyte globulin, sargramostim and busulfan
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2004to Jul 2009
- Phase
- Phase 1
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following advanced hematologic malignancies:
- Acute myeloid leukemia (AML) meeting the following criteria:
- Considered incurable with chemotherapy
- Marrow blasts ≤ 10% (may be achieved using standard chemotherapy regimen)
- Meets any of the following criteria:
- High-risk cytogenetics (-7, -7q, -5, -5q, t(6,9), t(9,11), complex [≥ 3 abnormalities], Philadelphia chromosome positive [Ph+])
- AML evolved from prior myelodysplasia
- AML secondary to prior chemotherapy
- Failed to achieve remission
- In second or subsequent remission
- Refractory relapse
- Myelodysplastic syndromes (MDS) meeting the following criteria:
- Must have high-risk features, including any of the following:
- Intermediate-2 or high risk International Prognostic Scoring System (IPSS) score
- Chronic myelomonocytic leukemia
- Marrow blasts ≤ 20% (chemotherapy may be given to achieve target blast levels)
- No rapidly progressive disease
- Acute lymphoblastic leukemia meeting the following criteria:
- Considered incurable with chemotherapy
- Meets any of the following criteria:
- High-risk cytogenetics (Ph+, t(4,11), 11q23 abnormalities, or monosomy 7)
- Required > 1 induction course to achieve remission
- Failed to enter remission
- In second or subsequent remission
- Marrow blasts ≤ 10% (chemotherapy may be given to achieve target blast levels)
- Chronic myelogenous leukemia (CML) meeting 1 of the following criteria:
- Chronic phase CML that failed imatinib mesylate therapy, as defined by progressive disease or failed to achieve a major cytogenetic response at 1 year after initiation of therapy
- Accelerated phase CML meeting 1 of the following criteria:
- Failed to achieve a complete cytogenetic remission at 1 year after initiation of therapy
- Failed to achieve any cytogenetic response after 6 months of therapy
- Progressive disease, as demonstrated by worsening cytogenetic response in 2 consecutive analyses separated by 4 weeks
- In blast crisis with < 10% blasts in bone marrow
- Multiple myeloma meeting the following criteria:
- Stage I-III disease
- Meets any of the following criteria:
- In relapse after autologous transplantation
- Refractory to ≥ 2 prior conventional myeloma therapies
- Chromosome 13 abnormalities (may be enrolled at diagnosis or after initial progression)
- Lymphoma
- The following subtypes are eligible:
- Diffuse large cell
- Follicular large cell
- Mantle cell
- Peripheral T-cell
- T-natural killer (T-NK) cell
- Hodgkin's lymphoma
- Must have progressed, recurred after prior therapy, or failed to respond to primary therapy
- Relapsed disease after autologous stem cell transplantation (SCT) allowed
- Low-grade non-Hodgkin's lymphoma meeting 1 of the following criteria:
- Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
- Relapsed after autologous SCT
- Chronic lymphocytic leukemia
- Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
- Relapsed after autologous SCT
- Meets 1 of the following criteria:
- Age 55-70 years
- Under age 55 and deemed ineligible for conventional high-dose chemotherapy, as indicated by any of the following:
- Poor cardiac function (i.e., LVEF < 40%)
- Poor pulmonary function (i.e., DLCO < 50%)
- Hepatic dysfunction
- Prior myeloablative therapy
- Not eligible for autologous SCT or conventional therapy
- Umbilical cord blood donor available
- Matched at ≥ 4 of 6 HLA antigens (A, B, and DR)
- Has 1-3 units of umbilical cord blood available
- Must not have an HLA-identical or 1 antigen mismatched related donor or potential HLA-matched unrelated donor readily available NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Creatinine clearance > 40 mL/min
- Creatinine < 2.0 mg/dL
- AST and alkaline phosphatase < 3 times upper limit of normal (ULN)
- Bilirubin < 2.0 mg/dL
- Hepatitis C or active hepatitis B virus (HBV) allowed if ≤ grade 2 fibrosis and/or inflammation by liver biopsy
- Patients with history of HBV infection should be tested for hepatitis B epsilon (HBe) antigen, anti-HBe, and HBV DNA (quantitative)
- Patients with active HBV viral replication should receive antiviral therapy
- Ejection fraction > 30%
- DLCO ≥ 40%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection requiring ongoing antibiotic treatment
- HIV negative
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Comprehensive Cancer Center
San Francisco, California, 94143-0324
About this study
Official title: Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients With Advanced Hematopoietic Malignancies
RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant helps stop both the growth of cancer cells and the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving chemotherapy, such as fludarabine and busulfan, and antithymocyte globulin before transplant and tacrolimus and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This clinical trial is studying how well giving low-dose fludarabine and busulfan together with anti-thymocyte globulin, followed by donor umbilical cord blood transplant works in treating patients with advanced hematologic cancer.
Read the detailed description
OBJECTIVES:
Primary
- Assess the feasibility of performing umbilical cord blood transplants in older patients or younger infirm patients with advanced hematologic malignancies using a reduced-intensity preparative regimen, as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100.
Secondary
- Describe the time to neutrophil and platelet recovery in patients treated with this regimen.
- Determine disease-specific, event-free, and overall survival rate at days 180 and 360.
- Determine the incidence, severity, and timing of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Evaluate T-cell, B-cell, and natural killer cell recovery in patients treated with this regimen.
- Assess lineage-specific chimerism after transplantation and describe the contribution of each individual cord blood unit to post-transplantation hematopoiesis.
OUTLINE: This is a pilot study.
- Reduced-intensity preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, busulfan IV over 2 hours 4 times daily on days -4 and -3, and anti-thymocyte globulin IV over 6 hours on days -3 to -1.
- Allogeneic umbilical cord blood transplantation: Patients undergo allogeneic umbilical cord blood transplant on day 0. Patients receive sargramostim (GM-CSF) subcutaneously or IV beginning on day 7 and continuing until blood counts recover.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally (as tolerated) beginning on day -2 and continuing for approximately 9 months. Patients also receive oral mycophenolate mofetil twice daily on days 1-50.
After completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
- Being tested
- anti-thymocyte globulin, sargramostim, busulfan, fludarabine phosphate, mycophenolate mofetil
- Keywords
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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), accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, angioimmunoblastic T-cell lymphoma, blastic phase chronic myelogenous leukemia, chronic myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, de novo myelodysplastic syndromes, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, anaplastic large cell lymphoma, nodal marginal zone B-cell lymphoma, previously treated myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent adult T-cell leukemia/lymphoma
- Medical subject headings
- Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Congenital Abnormalities, Leukemia, Myeloid, Accelerated Phase, Immunoblastic Lymphadenopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
sargramostimBiological
busulfanDrug
tacrolimusDrug
umbilical cord blood transplantationProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| cord blood transplant | Experimental | Not described Receives: Biological: anti-thymocyte globulin; Biological: sargramostim; Drug: busulfan; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: umbilical cord blood transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Feasibility of donor cord blood transplant
as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100
Measured: up to 36 months post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2006 (estimated)
- Study startSep 2004
- Primary completionJul 2009
- Study completionJul 2009
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 University of California, San FranciscoThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Thomas G. Martin, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00301951
- Sponsor's protocol ID
- CDR0000465362
- Other IDs
- UCSF-04253, UCSF-2407, UCSF-H24045-25271-02
- Status last verified
- Oct 2017
- First submitted
- 9 Mar 2006
- Last updated
- 12 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients With Advanced Hematopoietic Malignancies
- ClinicalTrials.gov ID
- NCT00301951
- Acronym / sponsor ID
- CDR0000465362
- Keywords
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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), accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2004
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 13 Mar 2006 (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 chemotherapy before a donor umbilical cord blood transplant helps stop both the growth of cancer cells and the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving chemotherapy, such as fludarabine and busulfan, and antithymocyte globulin before transplant and tacrolimus and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This clinical trial is studying how well giving low-dose fludarabine and busulfan together with anti-thymocyte globulin, followed by donor umbilical cord blood transplant works in treating patients with advanced hematologic cancer.
Detailed description
OBJECTIVES:
Primary
- Assess the feasibility of performing umbilical cord blood transplants in older patients or younger infirm patients with advanced hematologic malignancies using a reduced-intensity preparative regimen, as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100.
Secondary
- Describe the time to neutrophil and platelet recovery in patients treated with this regimen.
- Determine disease-specific, event-free, and overall survival rate at days 180 and 360.
- Determine the incidence, severity, and timing of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Evaluate T-cell, B-cell, and natural killer cell recovery in patients treated with this regimen.
- Assess lineage-specific chimerism after transplantation and describe the contribution of each individual cord blood unit to post-transplantation hematopoiesis.
OUTLINE: This is a pilot study.
- Reduced-intensity preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, busulfan IV over 2 hours 4 times daily on days -4 and -3, and anti-thymocyte globulin IV over 6 hours on days -3 to -1.
- Allogeneic umbilical cord blood transplantation: Patients undergo allogeneic umbilical cord blood transplant on day 0. Patients receive sargramostim (GM-CSF) subcutaneously or IV beginning on day 7 and continuing until blood counts recover.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally (as tolerated) beginning on day -2 and continuing for approximately 9 months. Patients also receive oral mycophenolate mofetil twice daily on days 1-50.
After completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cord blood transplant | Experimental | Biological: anti-thymocyte globulin, Biological: sargramostim, Drug: busulfan, Drug: fludarabine phosphate, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: umbilical cord blood transplantation |
Who may qualify
- Ages
- 18 to 70 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 |
|---|---|---|
| anti-thymocyte globulin | Biological | cord blood transplant |
| sargramostim | Biological | cord blood transplant |
| busulfan | Drug | cord blood transplant |
| fludarabine phosphate | Drug | cord blood transplant |
| mycophenolate mofetil | Drug | cord blood transplant |
| tacrolimus | Drug | cord blood transplant |
| umbilical cord blood transplantation | Procedure or surgery | cord blood transplant |
Primary outcome
Safety and Feasibility of donor cord blood transplant
Time frame: up to 36 months post transplant
as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100
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 12 Oct 2017.
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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.
Thomas G. Martin, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing anti-thymocyte globulin, sargramostim and busulfan in people with Leukemia and Lymphoma, run by University of California, San Francisco 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 12 Oct 2017. 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 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.
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?
Safety and Feasibility of donor cord blood transplant (time frame: up to 36 months post 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 12 Oct 2017.