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AzTrials

Chronic Myeloproliferative DisordersPhase 1NCT00255710

Cyclophosphamide and/or Mycophenolate Mofetil With or Without Tacrolimus in Treating Patients Who Are Undergoing a Donor Bone Marrow or Peripheral Stem Cell Transplant for Hematologic Cancer

A Phase 1 study testing filgrastim, cyclophosphamide and fludarabine phosphate in people with Chronic Myeloproliferative Disorders and Graft Versus Host Disease, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 fludarabine, and radiation therapy before a donor bone marrow or 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
What is being tested?
filgrastim, cyclophosphamide and fludarabine phosphate
Type of treatment
Surgery or procedure
How many people
60 participants
Where
1 siteUnited States
Study dates
Jul 2002to not given
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematologic malignancies:
  • Stage II or III multiple myeloma
  • Amyloidosis
  • Myelofibrosis with ≥ 2 of the following high-risk features:
  • Over 55 years of age
  • Hemoglobin < 10 g/dL
  • WBC < 3,000/mm^3 OR > 10,000/mm^3
  • Platelet count < 100,000/mm^3
  • Cytogenetic abnormalities
  • Mycosis fungoides, meeting 1 of the following criteria:
  • Stage IIB or III disease with evidence of histologic conversion to an aggressive lymphoma
  • Must demonstrate chemosensitivity
  • Stage IV disease
  • Paroxysmal nocturnal hemoglobinuria
  • Not meeting criteria for other bone marrow transplantation (BMT) or treatment studies
  • Diagnosis of 1 of the following hematologic malignancies, for which patient is not eligible for potentially curative allogeneic BMT due to end-organ dysfunction, age 65 to 75, or the amount of prior chemotherapy:
  • Acute myeloid or acute lymphoblastic leukemia
  • High-risk disease in first or second (or further) complete remission
  • Relapsed aggressive non-Hodgkin's lymphoma
  • Not eligible for autologous or standard allogeneic BMT
  • Hodgkin's lymphoma in second or further complete or partial remission
  • Not eligible for autologous or standard allogeneic BMT
  • Myelodysplastic syndromes or myelodysplastic/myeloproliferative diseases
  • Any of the following subtypes:
  • Refractory anemia with excess blasts (RAEB)
  • RAEB in transformation
  • Chronic myelomonocytic leukemia
  • Any morphologic subtype with multiple chromosomal abnormalities
  • Any subset with life-threatening cytopenias in all 3 cell lines, defined as platelet count ≤ 20,000/mm^3, absolute neutrophil count ≤ 500/mm^3, and reticulocyte count ≤ 50,000/mm^3
  • Meets both of the following criteria:
  • Less than 20% blasts by bone marrow biopsy
  • Not eligible for standard allogeneic BMT
  • No refractory anemia with ringed sideroblasts
  • No 5q syndrome
  • Stage III or IV chronic lymphocytic leukemia
  • Not meeting criteria for other BMT studies
  • Chronic myelogenous leukemia in first or second chronic phase
  • Not meeting criteria for other BMT studies or treatment
  • Stage III or IV indolent small lymphocytic or follicular lymphoma
  • Not eligible for autologous or standard allogeneic BMT or other active protocols at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Must have an HLA-identical related donor available

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin ≤ 3.0 mg/dL
  • AST ≤ 175 U/L
  • ALT ≤ 200 U/L

Renal

  • Creatinine ≤ 3.0 mg/dL

Cardiovascular

  • LVEF ≥ 30%

Pulmonary

  • FEV_1 ≥ 40% predicted
  • Forced vital capacity ≥ 40% predicted

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative

PRIOR CONCURRENT THERAPY:

Chemotherapy

  • See Disease Characteristics

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

Other trials in United States

About this study

Official title: Nonmyeloablative Bone Marrow Transplants in Hematologic Malignancies: Dose Finding Study for Post-Transplant Immunosuppression

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor bone marrow or 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 cyclophosphamide, mycophenolate mofetil, and tacrolimus after transplant may stop this from happening.

PURPOSE: This phase I trial is studying cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus to see which is the best regimen in treating patients who are undergoing a donor bone marrow or stem cell transplant for hematologic cancer.

Read the detailed description

OBJECTIVES:

  • Determine a minimal (short-duration) post-transplant immunosuppression regimen comprising cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus that results in ≤ 20% incidence of grade II or higher acute graft-versus-host disease (GVHD) in patients with hematologic malignancies undergoing nonmyeloablative allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-identical related donor.
  • Determine the post-transplant immunosuppression regimen that results in < 10% incidence of nonengraftment, defined as < 5% donor chimerism in peripheral blood at day 60, in these patients.
  • Determine the incidence and severity of acute GVHD in patients treated with these regimens.
  • Determine the frequency of mixed chimerism in patients treated with these regimens.

OUTLINE:

  • Nonmyeloablative allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT): Patients receive fludarabine IV on days -4 to -2 and undergo total-body irradiation on day -1. Patients undergo allogeneic BMT on day 0 or PBSCT on day 0 (and days 1 and 2, if needed). Patients receive filgrastim (G-CSF) beginning on day 5 and continuing until at least day 15 or until blood counts recover.
  • Sequentially increasing levels of post-transplant immunosuppression: Cohorts of patients are enrolled into 1 of the following regimens:
  • Regimen 1 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on day 3 only.
  • Regimen 2 (post-BMT immunosuppression): Patients receive mycophenolate mofetil (MMF) once on day 3 and then twice daily on days 4-32.
  • Regimen 3 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on days 3 and 4 and MMF twice daily on days 4-33.
  • Regimen 4 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3.
  • Regimen 5 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3 and tacrolimus twice daily on days 4-33.

Cohorts of approximately 10-20 patients receive sequentially increasing levels of post-transplant immunosuppression until a minimal (short-duration) post-transplant immunosuppression regimen is identified. The minimal post-transplant immunosuppression regimen is defined as the regimen in which ≤ 3 of 10 or ≤ 6 of 20 patients develop grade II or higher acute graft-versus-host disease AND ≤ 2 of 10 or ≤ 4 of 20 patients fail to engraft 60 days post-transplantation. Once the minimal post-transplant immunosuppression regimen is identified, an additional 10 patients are treated with that regimen.

Patients are followed for 60 days after transplantation.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Keywords
graft versus host disease, 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), adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, chronic idiopathic myelofibrosis, chronic myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, previously treated myelodysplastic syndromes, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma
Medical subject headings
Myeloproliferative Disorders, Graft vs Host Disease, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases

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. Post-transplant immunosuppression regimen with ≤ 20% incidence of a grade II-IV graft-versus-host-disease (GVHD) and < 10% incidence of nonengraftment (< 5% donor chimerism) at day 60 following transplant

  2. Incidence and severity of acute GVHD at day 60 following transplant

  3. Frequency of mixed chimerism defined as any detectable donor cells at day 60 following transplant

Timeline

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

  1. First posted21 Nov 2005 (estimated)
  2. Study startJul 2002

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 1
Primary purpose
Supportive care
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00255710
Sponsor's protocol ID
CDR0000449652
Other IDs
P01CA015396, P30CA006973, JHOC-J0169, WIRB-20020304
Status last verified
Mar 2010
First submitted
18 Nov 2005
Last updated
17 Mar 2010
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing filgrastim, cyclophosphamide and fludarabine phosphate in people with Chronic Myeloproliferative Disorders and Graft Versus Host Disease, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 17 Mar 2010. 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?

Post-transplant immunosuppression regimen with ≤ 20% incidence of a grade II-IV graft-versus-host-disease (GVHD) and < 10% incidence of nonengraftment (< 5% donor chimerism) at day 60 following transplant. The study lists 3 primary outcomes in all. 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 NCT00255710.

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 17 Mar 2010.

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