Chronic Myeloproliferative DisordersNCT00296023
Donor Stem Cell Transplant in Treating Older or Frail Patients With Hematologic Cancer
A study testing anti-thymocyte globulin, filgrastim and therapeutic allogeneic lymphocytes in people with Chronic Myeloproliferative Disorders and Leukemia, run by University of California, San Francisco at 2 sites in United States.
Trial summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or 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?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
- What is being tested?
- anti-thymocyte globulin, filgrastim and therapeutic allogeneic lymphocytes
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 1999to Jun 2008
- Phase
- Interventional
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of a high-risk indolent hematologic malignancy meeting the following criteria:
- Chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria:
- In second or subsequent remission
- Failed to achieve a complete remission (CR) after chemotherapy
- Non-Hodgkin's lymphoma (NHL) meeting 1 of the following criteria:
- Low-grade NHL meeting 1 of the following criteria:
- Standard-risk disease in second or subsequent remission
- Standard-risk disease and failed to achieve a CR after chemotherapy
- In first or subsequent remission with adverse International Prognostic Index (IPI) prognostic features, as defined by the presence of ≥ 3 of the following:
- Age > 60 years
- Tumor stage III or IV
- Extranodal disease at > 1 site
- ECOG performance status ≥ 2
- Serum lactic dehydrogenase (LDH) > upper limit of normal (ULN)
- Intermediate- or high-grade NHL meeting 1 of the following criteria:
- In second or subsequent remission
- Failed to achieve a CR after initial chemotherapy
- Waldenstrom's macroglobulinemia meeting 1 of the following criteria:
- In second or subsequent remission
- Failed to achieve a CR after initial chemotherapy
- Multiple myeloma meeting 1 of the following criteria:
- In first or subsequent remission
- Failed to achieve a CR after initial chemotherapy
- Myeloproliferative disorders, including any of the following:
- Chronic myelogenous leukemia in first or subsequent chronic phase
- Myelofibrosis
- Essential thrombocytopenia that is poorly responsive to standard therapy
- Polycythemia vera that is poorly responsive to standard therapy or is in spent phase
- Prolymphocytic leukemia meeting 1 of the following criteria:
- In first or subsequent remission
- Failed to achieve a CR after initial chemotherapy
- Mantle cell lymphoma meeting 1 of the following criteria:
- In first or subsequent remission
- Failed to achieve a CR after initial chemotherapy
- Hodgkin's lymphoma meeting the following criteria:
- In second or subsequent remission
- Prior remission duration > 6 months
- No radiation therapy as the only prior primary therapy
- Myelodysplastic syndromes (MDS) meeting 1 of the following criteria:
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Chronic myelomonocytic leukemia
- Any MDS with transfusion dependence
- Any MDS with ≥ 2 significant infections
- Acute myeloid leukemia in morphologic remission
- In CR or partial remission or stabilization of disease after standard chemotherapy
- No progressive or refractory disease
- Not eligible for standard allogeneic bone marrow transplantation
- Meets 1 of the following criteria:
- Age 60 to 75 years old AND no co-morbid illness
- Younger patients with any of the following comorbidities:
- Decreased cardiac ejection fraction
- Pulmonary dysfunction
- Elevated liver function tests
- Hepatitis C infection
- Poor performance status
- Sibling or related donor available
- Matched ≥ 5/6 HLA loci (A, B, and DR) 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:
- See Disease Characteristics
- ECOG performance status 0-2
- Creatinine < 2.0 mg/dL
- Creatinine clearance > 40 mL/min
- Ejection fraction > 30% by echocardiogram or MUGA
- Bilirubin < 3.0 mg/dL (if total bilirubin is elevated and Gilbert's disease is suspected, direct bilirubin must be normal)
- Alkaline phosphatase < 4 times ULN
- AST < 4 times ULN
- HIV negative
- Hepatitis B and/or C virus allowed if a liver biopsy (performed within the past 3 months) shows ≤ grade 2 inflammation
- No active infection
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Alta Bates Comprehensive Cancer Center
Berkeley, California, 94704
UCSF Comprehensive Cancer Center
San Francisco, California, 94143-0324
About this study
Official title: Low-Dose Allogeneic Peripheral Blood Stem Cell Transplantation for High-Risk Low Grade Hematologic Malignancies
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or 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) 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 antithymocyte globulin before transplant and methotrexate and tacrolimus after the transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in treating older or frail patients with hematologic cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the safety of non-myeloablative allogeneic peripheral blood stem cell transplantation, in terms of regimen-related organ toxicity and toxicity from acute graft-vs-host disease (GVHD), in older or medically frail patients with high-risk indolent hematologic malignancies.
- Determine overall survival, disease-free survival, and relapse risk at 1, 2, and 3 years post-transplantation in these patients.
Secondary
- Determine the engraftment of donor hematopoiesis at 6 weeks, 3 and 6 months, and 1 year post-transplantation in these patients.
- Determine the incidence and severity of chronic GVHD in older and medically infirm patients treated with this regimen.
- Determine the safety and efficacy of collecting peripheral blood stem cells from older donors (age > 60 years).
- Determine the need and efficacy of donor lymphocyte infusions in patients with residual disease after transplant.
OUTLINE:
- Non-myeloablative preparative regimen:Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours every 8 hours on days -4 and -3, and anti-thymocyte globulin IV over 8 hours on days -4 to -1.
- Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus orally every 12 hours or IV continuously beginning on day -2 and continuing until day 90, followed by a taper until day 180. Patients also receive methotrexate IV over 15-30 minutes on days 1, 3, 6, and 11.
- Donor lymphocyte infusions (DLIs): Patients with residual disease ≥ 6 months post-transplantation who are off immunosuppression for ≥ 30 days with no evidence of GVHD may receive DLIs. DLIs are administered ≥ 12 weeks apart in the presence of persistent disease, absence of severe (grade 3-4) GVHD, and absence of persistent GVHD after the first DLI.
After completion of study therapy, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Being tested
- anti-thymocyte globulin, filgrastim, therapeutic allogeneic lymphocytes, busulfan, fludarabine phosphate
- Keywords
- stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, noncontiguous stage II marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, noncontiguous stage II adult Burkitt lymphoma
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
filgrastimBiological
therapeutic allogeneic lymphocytesBiological
busulfanDrug
methotrexateDrug
tacrolimusDrug
nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| stem cell transplant | Experimental | Not described Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Biological: therapeutic allogeneic lymphocytes; Drug: busulfan; Drug: fludarabine phosphate; Drug: methotrexate; Drug: tacrolimus; Procedure: nonmyeloablative 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.
Toxicity and survival
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 posted24 Feb 2006 (estimated)
- Study startJan 1999
- Primary completionJun 2007
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloproliferative DisordersStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 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 FranciscoWillis Navarro, MD, Principal investigator, University of California, San FranciscoCharles A. Linker, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00296023
- Sponsor's protocol ID
- CDR0000463724
- Other IDs
- UCSF-98251, UCSF-9805, UCSF-H9996-15837-06
- Status last verified
- Oct 2012
- First submitted
- 23 Feb 2006
- Last updated
- 4 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-Dose Allogeneic Peripheral Blood Stem Cell Transplantation for High-Risk Low Grade Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00296023
- Acronym / sponsor ID
- CDR0000463724
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Keywords
- stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 1999
- Primary completion
- Jun 2007 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 24 Feb 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 low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or 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) 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 antithymocyte globulin before transplant and methotrexate and tacrolimus after the transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in treating older or frail patients with hematologic cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the safety of non-myeloablative allogeneic peripheral blood stem cell transplantation, in terms of regimen-related organ toxicity and toxicity from acute graft-vs-host disease (GVHD), in older or medically frail patients with high-risk indolent hematologic malignancies.
- Determine overall survival, disease-free survival, and relapse risk at 1, 2, and 3 years post-transplantation in these patients.
Secondary
- Determine the engraftment of donor hematopoiesis at 6 weeks, 3 and 6 months, and 1 year post-transplantation in these patients.
- Determine the incidence and severity of chronic GVHD in older and medically infirm patients treated with this regimen.
- Determine the safety and efficacy of collecting peripheral blood stem cells from older donors (age > 60 years).
- Determine the need and efficacy of donor lymphocyte infusions in patients with residual disease after transplant.
OUTLINE:
- Non-myeloablative preparative regimen:Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours every 8 hours on days -4 and -3, and anti-thymocyte globulin IV over 8 hours on days -4 to -1.
- Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus orally every 12 hours or IV continuously beginning on day -2 and continuing until day 90, followed by a taper until day 180. Patients also receive methotrexate IV over 15-30 minutes on days 1, 3, 6, and 11.
- Donor lymphocyte infusions (DLIs): Patients with residual disease ≥ 6 months post-transplantation who are off immunosuppression for ≥ 30 days with no evidence of GVHD may receive DLIs. DLIs are administered ≥ 12 weeks apart in the presence of persistent disease, absence of severe (grade 3-4) GVHD, and absence of persistent GVHD after the first DLI.
After completion of study therapy, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| stem cell transplant | Experimental | Biological: anti-thymocyte globulin, Biological: filgrastim, Biological: therapeutic allogeneic lymphocytes, Drug: busulfan, Drug: fludarabine phosphate, Drug: methotrexate, Drug: tacrolimus, Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation, Procedure: peripheral blood stem cell transplantation |
Who may qualify
- Ages
- 18 to 75 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 | stem cell transplant |
| filgrastim | Biological | stem cell transplant |
| therapeutic allogeneic lymphocytes | Biological | stem cell transplant |
| busulfan | Drug | stem cell transplant |
| fludarabine phosphate | Drug | stem cell transplant |
| methotrexate | Drug | stem cell transplant |
| tacrolimus | Drug | stem cell transplant |
| nonmyeloablative allogeneic hematopoietic stem cell transplantation | Procedure or surgery | stem cell transplant |
| peripheral blood stem cell transplantation | Procedure or surgery | stem cell transplant |
Primary outcome
Toxicity and survival
Time frame: up to 36 months post transplant
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 4 Oct 2012.
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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
Willis Navarro, MD principal investigator
University of California, San Francisco
Charles A. Linker, MD principal investigator
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing anti-thymocyte globulin, filgrastim and therapeutic allogeneic lymphocytes in people with Chronic Myeloproliferative Disorders and Leukemia, run by University of California, San Francisco at 2 sites 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 4 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
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?
Toxicity and survival (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 4 Oct 2012.