Myeloproliferative DisordersPhase 2NCT00827099
Umbilical Cord Blood (UCB) Transplant, Fludarabine, Melphalan, and Anti-thymocyte Globulin (ATG) in Treating Patients With Hematologic Cancer
A Phase 2 study testing anti-thymocyte globulin, fludarabine phosphate and Melphalan in people with Myeloproliferative Disorders and Leukemia, run by Northside Hospital, Inc. at 1 site in United States.
Trial summary
RATIONALE: Giving low doses of chemotherapy before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Myeloproliferative Disorders, Leukemia, Lymphoma
- What is being tested?
- anti-thymocyte globulin, fludarabine phosphate and Melphalan
- Type of treatment
- Surgery or procedure
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Nov 2009
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of hematologic malignancy for which a reduced-intensity allogeneic stem cell transplantation is deemed clinically appropriate, including any of the following:
- Chronic myelogenous leukemia, meeting one of the following criteria:
- In first chronic phase AND failed imatinib mesylate therapy, defined as failure to obtain a hematologic remission by 3 months or major cytogenetic response (Ph+ cells < 35%) by 12 months, or demonstrated clonal evolution or disease progression while on therapy
- In accelerated phase with < 15% blasts
- In blast crisis that has entered into a second chronic phase following induction chemotherapy
- Acute myelogenous leukemia, meeting one of the following criteria:
- In second or subsequent completion remission*
- Failed primary induction chemotherapy, but subsequently entered into a complete remission* with ≤ 2 subsequent re-induction chemotherapy treatment(s)
- In first complete remission* with poor-risk cytogenetics NOTE: *Complete remission is defined as < 5% blasts in bone marrow, no definitive evidence of disease by morphology, flow cytometry, or genetic studies, and no circulating blasts. Neutrophil and platelet count recovery will not be required.
- Acute lymphoblastic leukemia, meeting one of the following criteria:
- In second or subsequent complete remission
- In first complete remission AND t(9;22)
- Myelodysplastic syndromes, meeting the following criteria:
- High-risk disease, defined as International Prognostic Scoring System score of ≥ 1.5
- Less than 10% blasts at the time of study enrollment
- Chronic myelomonocytic leukemia
- Less than 10% blasts at the time of study enrollment
- Myeloid metaplasia with myelofibrosis with poor-risk features, meeting one of the following criteria:
- Age < 55 years AND a Lille score of 1
- Lille score of 2
- Hemoglobin < 10 g/dL AND abnormal karyotype
- Chronic lymphocytic leukemia/prolymphocytic leukemia, meeting all of the following criteria:
- Rai stage I-IV disease
- Failed ≥ 1 prior chemotherapy regimen, including fludarabine, or autologous stem cell transplantation
- Chemosensitive or stable, non-bulky disease prior to transplant
- Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens)
- Low-grade B-cell non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma, follicular center [grade 1 or 2] lymphoma, or marginal zone lymphoma), meeting all of the following criteria:
- Failed ≥ 1 prior chemotherapy regimen or autologous stem cell transplantation
- Chemosensitive or stable, non-bulky disease prior to transplant
- Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens)
- Intermediate-grade B-cell or T-cell NHL or mantle cell NHL, meeting all of the following criteria:
- Failed to achieve remission or recurred after either conventional chemotherapy or autologous stem cell transplantation
- Chemosensitive, non-bulky disease prior to transplant
- Hodgkin lymphoma, meeting all of the following criteria:
- Relapsed after prior autologous stem cell transplantation or after ≥ 2 combination chemotherapy regimens AND ineligible for autologous peripheral blood stem cell transplantation
- Chemosensitive, non-bulky disease prior to transplant
- Multiple myeloma, meeting one of the following criteria:
- Relapsed after autologous stem cell transplantation
- Relapsed after conventional therapies AND not a candidate for autologous stem cell transplantation
- No HLA-matched related or unrelated donor available
- Has two umbilical cord blood units available that are matched at ≥ 4/6 HLA A, B, and DRB1 with the patient and with each other (HLA C and DQ will not be used in the match strategy)
- Total combined nucleated cell dose from the 2 umbilical cord blood units must be > 3.7 x 10^7 nucleated cells/kg (pre-freeze dose) 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:
- Karnofsky performance status 80-100%
- Adapted, weighted Charlson Comorbidity Index < 3
- Serum creatinine ≤ 2.0 mg/dL
- AST or ALT < 3 times upper limit of normal (ULN)
- Bilirubin < 1.5 times ULN
- Not pregnant or nursing
- LVEF ≥ 40%
- DLCO > 50%
- No hypoxia at rest with oxygen saturation < 92% on room air (corrected with bronchodilator therapy)
- No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral infection)
- No active hepatitis B or C infection that, in the opinion of a gastroenterologist or the transplant committee, places the patient at moderate- to high-risk for developing severe hepatic disease
- No HIV infection
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial locations and contacts
1 site in 1 country.
United States1 site
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342
About this study
Official title: Transplantation of Two Partially Matched Umbilical Cord Blood Units Following Reduced Intensity Conditioning to Enhance Engraftment and Limit Transplant-Related Mortality in Adults With Hematologic Malignancies
RATIONALE: Giving low doses of chemotherapy before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop 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 tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving umbilical cord blood transplant together with fludarabine, melphalan, and antithymocyte globulin works in treating patients with hematologic cancer.
Read the detailed description
OBJECTIVES:
Primary
- To evaluate the 100-day transplant-related (non-relapse) mortality in patients with hematologic malignancies undergoing reduced-intensity conditioning comprising fludarabine phosphate, melphalan, and anti-thymocyte globulin followed by sequential umbilical cord blood transplantation (UCBT) from 2 partially-matched unrelated donors.
Secondary
- To evaluate the 12-month transplant-related (non-relapse) mortality.
- To evaluate the days to neutrophil engraftment (ANC > 500/mm³).
- To evaluate the days to platelet engraftment (platelet count > 20,000/mm³ [unsupported]).
- To evaluate the risk of acute and chronic graft-vs-host disease.
- To evaluate percent donor chimerism contribution of each cord unit.
- To evaluate relapse rate.
- To evaluate disease-free and overall survival.
- To evaluate transfusion support needed for UCBT recipients.
OUTLINE:
- Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3, melphalan IV over 30-60 minutes on day -2, and anti-thymocyte globulin IV over 4-6 hours on days -4 to -2.
- Transplantation: Patients undergo two sequential umbilical cord blood transplantations on day 0.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously and then orally twice daily beginning on day -1 and continuing until day 60, followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day 0 and continuing until day 30, followed by a taper until day 60 in the absence of GVHD.
After completion of study treatment, patients are followed periodically.
- Conditions
- Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Being tested
- anti-thymocyte globulin, fludarabine phosphate, Melphalan, mycophenolate mofetil, tacrolimus
- Keywords
- accelerated phase cml, adult ALL in remission, adult AML in remission, adult AML with 11q23 (MLL) abnormalities, adult AML 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), blastic phase chronic myelogenous leukemia, chronic myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, prolymphocytic leukemia, recurrent adult T-cell leukemia/lymphoma, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, refractory chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
anti-thymocyte globulin
fludarabine phosphate
MelphalanDrug
melphalan
mycophenolate mofetil
tacrolimusDrug
tacrolimus
umbilical cord blood transplantationProcedure or surgery
umbilical cord blood transplantation
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With 100 Day Transplant-related Mortality (TRM)
100 Day TRM is death within 100 days from transplant related complications
Measured: 100 days
Secondary outcomes (5)
Number of Patients That Engrafted Blood Counts by 30 Days After Transplant
Number of patients whose Absolute Neutrophil Count (ANC) recovered to >500 x10^3/uL for at least 3 consecutive days after transplant
Measured: Day 30
Percentage of Donor and Host Chimerism of Each Cord Blood Unit
Evaluate the percentages of donor and host chimerism at multiple times post-transplant including Day 30, Day 60, Day 90 and monthly thereafter if the patient is not considered to have full chimerism.
Measured: day 30, day 60, day 90
Number of Patients Who Experience Acute and Chronic Graft-vs-host Disease After Transplant.
Patients will be evaluated regularly for the development of graft versus host disease both acute \& chronic.
Measured: Day 30
Number of Patients Who Experience Disease Relapse Post-transplant
Patients will have routine restaging to assess disease response at Day 100, 6 months, 1 year, 18 months and 24 months. If disease relapse is suspected, the patient will be evaluated at that time.
Measured: Day 100, 6 months, 1 year, 18 months, 24 months
Number of Patients Who Survive Following Treatment on This Protocol
Patients will be followed until death
Measured: Through Death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2009 (estimated)
- Study startJun 2006
- Primary completionNov 2009
- Study completionNov 2009
Why it stopped: Unacceptable morbidity \& mortality
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 Myeloproliferative DisordersStudies of the same condition, open and under way.
- 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northside Hospital, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Scott R. Solomon, MD, Principal investigator, Blood and Marrow Transplant Group of Georgia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00827099
- Sponsor's protocol ID
- CDR0000632453
- Other IDs
- BMTGG-NSH-801
- Status last verified
- Mar 2012
- First submitted
- 21 Jan 2009
- Last updated
- 23 Mar 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transplantation of Two Partially Matched Umbilical Cord Blood Units Following Reduced Intensity Conditioning to Enhance Engraftment and Limit Transplant-Related Mortality in Adults With Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00827099
- Acronym / sponsor ID
- CDR0000632453
- Conditions
- Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Keywords
- accelerated phase cml, adult ALL in remission, adult AML in remission, adult AML with 11q23 (MLL) abnormalities, adult AML 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)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unacceptable morbidity \& mortality
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Northside Hospital, Inc.University, hospital or other
- Study start
- Jun 2006
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 22 Jan 2009 (estimated)
- Results
- Posted 3 Aug 2011
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 before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop 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 tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving umbilical cord blood transplant together with fludarabine, melphalan, and antithymocyte globulin works in treating patients with hematologic cancer.
Detailed description
OBJECTIVES:
Primary
- To evaluate the 100-day transplant-related (non-relapse) mortality in patients with hematologic malignancies undergoing reduced-intensity conditioning comprising fludarabine phosphate, melphalan, and anti-thymocyte globulin followed by sequential umbilical cord blood transplantation (UCBT) from 2 partially-matched unrelated donors.
Secondary
- To evaluate the 12-month transplant-related (non-relapse) mortality.
- To evaluate the days to neutrophil engraftment (ANC > 500/mm³).
- To evaluate the days to platelet engraftment (platelet count > 20,000/mm³ [unsupported]).
- To evaluate the risk of acute and chronic graft-vs-host disease.
- To evaluate percent donor chimerism contribution of each cord unit.
- To evaluate relapse rate.
- To evaluate disease-free and overall survival.
- To evaluate transfusion support needed for UCBT recipients.
OUTLINE:
- Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3, melphalan IV over 30-60 minutes on day -2, and anti-thymocyte globulin IV over 4-6 hours on days -4 to -2.
- Transplantation: Patients undergo two sequential umbilical cord blood transplantations on day 0.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously and then orally twice daily beginning on day -1 and continuing until day 60, followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day 0 and continuing until day 30, followed by a taper until day 60 in the absence of 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)
Who may qualify
- Ages
- 18 to 65 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 globulinanti-thymocyte globulin | Biological | – |
| fludarabine phosphatefludarabine phosphate | Drug | – |
| Melphalanmelphalan | Drug | – |
| mycophenolate mofetilmycophenolate mofetil | Drug | – |
| tacrolimustacrolimus | Drug | – |
| umbilical cord blood transplantationumbilical cord blood transplantation | Procedure or surgery | – |
Primary outcome
Number of Participants With 100 Day Transplant-related Mortality (TRM)
Time frame: 100 days
100 Day TRM is death within 100 days from transplant related complications
5 secondary outcomes
Number of Patients That Engrafted Blood Counts by 30 Days After Transplant
Time frame: Day 30
Percentage of Donor and Host Chimerism of Each Cord Blood Unit
Time frame: day 30, day 60, day 90
Number of Patients Who Experience Acute and Chronic Graft-vs-host Disease After Transplant.
Time frame: Day 30
Number of Patients Who Experience Disease Relapse Post-transplant
Time frame: Day 100, 6 months, 1 year, 18 months, 24 months
Number of Patients Who Survive Following Treatment on This Protocol
Time frame: Through Death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2012.
- 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.
Scott R. Solomon, MD principal investigator
Blood and Marrow Transplant Group of Georgia
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 anti-thymocyte globulin, fludarabine phosphate and Melphalan in people with Myeloproliferative Disorders and Leukemia, run by Northside Hospital, Inc. 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: stopped early, as of the sponsor's last update on 23 Mar 2012. 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 3 Aug 2011). 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 Participants With 100 Day Transplant-related Mortality (TRM) (time frame: 100 days). 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 23 Mar 2012.