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Chronic Myeloproliferative DisordersNCT00290641

Chemotherapy and Total-Body Irradiation Followed by Donor Umbilical Cord Blood Transplant, Cyclosporine, and Mycophenolate Mofetil in Treating Patients With Hematologic Cancer

A study testing filgrastim, graft-versus-tumor induction therapy and cyclophosphamide in people with Chronic Myeloproliferative Disorders and Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, and radiation therapy before a donor umbilical cord 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 Up to 45 years
What is being tested?
filgrastim, graft-versus-tumor induction therapy and cyclophosphamide
Type of treatment
Surgery or procedure
How many people
68 participants
Where
1 siteUnited States
Study dates
Apr 2001to Jan 2006
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 Up to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Diagnosis of a hematologic malignancy of 1 of the following types:
  • Acute myeloid leukemia (AML), meeting the following criteria:
  • In complete remission (CR) by morphology (< 5% blasts in the bone marrow), as defined by 1 of the following:
  • In first CR (CR1) and meets ≥ 1 of the following high-risk criteria:
  • High-risk cytogenetics (e.g., those associated with myelodysplastic syndromes [MDS] or complex karotype)
  • Preceding MDS
  • More than 2 courses of therapy was required to obtain CR
  • In second or greater CR
  • No morphologic relapse
  • Cytogenetic relapse or persistent disease allowed
  • Acute lymphocytic leukemia (ALL), meeting the following criteria:
  • In CR, as defined by 1 of the following:
  • In CR1 and meets ≥ 1 of the following high-risk criteria:
  • Unfavorable high-risk cytogenetics [t(9;22), t(1;19), t(4;11) or other MLL rearrangements]
  • More than 1 course of therapy was required to obtain CR
  • In second or greater CR
  • No morphologic relapse or persistent disease
  • Chronic myelogenous leukemia (CML), excluding refractory blast crisis
  • Advanced myelofibrosis
  • Advanced myelodysplasia (blasts < 10% [otherwise need AML induction pre-transplant]), meeting ≥ 1 of the following criteria:
  • Refractory anemia with excess blasts (RAEB)
  • RAEB in transformation
  • Refractory anemia with severe pancytopenia
  • High-risk cytogenetics
  • Non-Hodgkin's lymphoma (NHL), meeting the following criteria:
  • One of the following histologic subtypes:
  • Mantle cell NHL
  • Disease progression after initial therapy (e.g., CHOP)
  • Beyond CR1 or beyond first partial remission (PR)
  • Intermediate-grade NHL in second or greater CR or PR
  • High-grade NHL
  • Stage III or IV disease AND received initial therapy
  • Stage I or II disease at diagnosis that subsequently progressed after a prior response duration of < 1 year
  • No chemotherapy-refractory NHL (i.e., < progressive disease after > 2 salvage regimens)
  • Donor available, meeting the following criteria:
  • No other existing HLA-identical related donor available
  • 4-6/6 HLA-A, -B, and -DRB1, matched unrelated donor by molecular techniques
  • A and B to antigen level resolution
  • DR to allele resolution
  • Umbilical cord blood (UCB) graft may consist of one or two UCB units 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 score 80-100% (for adults) OR
  • Lansky score 50-100% (for children)
  • Creatinine ≤ 2.0 mg/dL (for adults) OR creatinine clearance > 40 mL/min (for children)
  • Adults with a creatinine > 1.2 mg/dL or a history of renal dysfunction must have a creatinine clearance > 40 mL/min
  • Bilirubin ≤ 2 times normal
  • AST and ALT ≤ 2 times normal
  • Alkaline phosphatase ≤ 2 times normal
  • Pulmonary function > 50 % of normal
  • LVEF ≥ 45%
  • No active infection, including Aspergillus or other mold, within the past 30 days
  • No history of HIV infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior myeloablative transplant within the past 6 months if ≤ 18 years old
  • No prior myeloablative allotransplant or autologous transplant if > 18 years old
  • No prior extensive therapy (e.g., > 12 months of alkylating therapy or > 6 months of alkylating therapy with extensive radiation)

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Minnesota Cancer Center

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: A Cyclophosphamide/Fludarabine/Total Body Irradiation Preparative Regimen for Patients With Hematological Malignancy Receiving Unrelated Donor Umbilical Cord Blood Transplantation

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, and radiation therapy before a donor umbilical cord 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). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving chemotherapy together with total-body irradiation followed by donor umbilical cord blood transplant, cyclosporine, and mycophenolate mofetil works in treating patients with hematologic cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the engraftment potential of unrelated allogeneic umbilical cord blood (UCB) using nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil in patients with hematologic malignancies.

Secondary

  • Determine the rate of neutrophil and platelet recovery and the completeness of donor cell engraftment in patients treated with this regimen.
  • Determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD) in patients treated with this regimen.
  • Determine the incidence of malignant relapse in patients treated with this regimen.
  • Determine the 1- and 2-year survival and event-free survival of patients treated with this regimen.
  • Determine the phenotype and function of immune cells recovering after UCB transplantation in patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: Patients are stratified according to HLA disparity (0-1 vs 2) and number of graft units (1 vs 2).

  • Nonmyeloablative conditioning: Patients receive nonmyeloablative conditioning comprising fludarabine IV over 1 hour on days -8 to -6 and cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total-body irradiation twice daily on days -4 to -1.
  • Unrelated allogeneic umbilical cord blood transplantation (UCBT): Patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
  • Immunosuppression: Patients receive cyclosporine orally or IV over 2 hours 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper in the absence of graft-vs-host disease (GVHD). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 30, continuing beyond day 30 if no donor engraftment. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Being tested
filgrastim, graft-versus-tumor induction therapy, cyclophosphamide, cyclosporine, fludarabine phosphate
Keywords
adult acute myeloid leukemia in remission, 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), childhood acute myeloid leukemia in remission, secondary acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, refractory anemia with excess blasts, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, noncontiguous stage II adult Burkitt lymphoma, recurrent adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma
Medical subject headings
Myeloproliferative Disorders, Leukemia, Lymphoma, Myelodysplastic Syndromes, Congenital Abnormalities, Leukemia, Myeloid, Accelerated Phase, Leukemia, Myeloid, Chronic-Phase, Anemia, Refractory, with Excess of Blasts

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Engraftment as measured by an absolute neutrophil count of donor origin > 0.5 x 109 /L for 3 days by day 42

Secondary outcomes (2)
  1. Incidence and severity of acute or chronic graft-versus-host-disease, relapse, or mortality at day 100

  2. Survival and event-free survival by Kaplan-Meier estimation at 1 and 2 years after umbilical cord blood (UCB) transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Feb 2006 (estimated)
  2. Study startApr 2001
  3. Primary completionJan 2006
  4. Study completionJan 2006

Resources

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
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00290641
Sponsor's protocol ID
2000LS068
Other IDs
MT2000-25
Status last verified
Nov 2017
First submitted
9 Feb 2006
Last updated
29 Nov 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS, Verfaillie CM, Wagner JE. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005 Feb 1;105(3):1343-7. doi: 10.1182/blood-2004-07-2717. Epub 2004 Oct 5.

    PubMed 15466923

Questions about this trial

What is this clinical trial studying?

A study testing filgrastim, graft-versus-tumor induction therapy and cyclophosphamide in people with Chronic Myeloproliferative Disorders and Leukemia, run by Masonic Cancer Center, University of Minnesota 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 29 Nov 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.

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?

Engraftment as measured by an absolute neutrophil count of donor origin > 0.5 x 109 /L for 3 days by day 42. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00290641, which also lists 1 linked publication.

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 29 Nov 2017.

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