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Accelerated Phase Chronic Myelogenous LeukemiaPhase 1/2NCT00078858

Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant

A Phase 1/2 study testing fludarabine phosphate, total-body irradiation and nonmyeloablative allogeneic hematopoietic stem cell transplantation in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Center at 10 sites in 3 countries.

Completed

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

Official record
Search all trials

Trial summary

This phase I/II trial studies whether stopping cyclosporine before mycophenolate mofetil is better at reducing the risk of life-threatening graft-versus-host disease (GVHD) than the previous approach where mycophenolate mofetil was stopped before cyclosporine. Read more about this study

Who is it for?
Any age
What is being tested?
fludarabine phosphate, total-body irradiation and nonmyeloablative allogeneic hematopoietic stem cell transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
10 sitesin 3 countries
Study dates
Sep 2003to Jan 2006
Phase
Phase 1/2
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Ages > 50 years with hematologic malignancies treatable by unrelated HCT
  • Ages =< 50 years of age with hematologic diseases treatable by allogeneic HCT who through pre-existing medical conditions or prior therapy are considered to be at high risk for regimen related toxicity associated with a conventional transplant (> 40% risk of transplant-related mortality [TRM]) or those patients who refuse a conventional HCT; transplants must be approved for these inclusion criteria by both the participating institution's patient review committee such as the Patient Care Conference (PCC at the Fred Hutchinson Cancer Research Center [FHCRC]) and by the principal investigator at the collaborating center; patients =< 50 years of age who have received previous high-dose transplantation do not require patient review committee approval; all children < 12 years must be discussed with the FHCRC primary investigator (PI) prior to registration
  • Patients with metastatic renal cell carcinoma with the histologic subtypes of clear cell, papillary and medullary may be accepted regardless of age
  • The following diseases will be permitted although other diagnoses can be considered if approved by PCC or the participating institution's patient review committees and the principal investigator:
  • Aggressive non-Hodgkin lymphomas (NHLs) and other histologies such as diffuse large B cell NHL-not eligible for autologous hematopoietic stem cell transplant (HSCT), not eligible for conventional myeloablative HSCT, or after failed autologous HSCT
  • Low grade NHL- with < 6 month duration of complete remission (CR) between courses of conventional therapy
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  • Mantle cell NHL-may be treated in first CR
  • Chronic lymphocytic leukemia (CLL)- Must be refractory to fludarabine; patients who fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-cladribine [CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)
  • Hodgkin disease (HD)- must have received and failed frontline therapy
  • Multiple myeloma (MM)- must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted
  • Acute myeloid leukemia (AML)- must have < 5% marrow blasts at the time of transplant.
  • Acute lymphocytic leukemia (ALL)- must have < 5% marrow blasts at the time of transplant
  • Chronic myelogenous leukemia (CML)- Patients will be accepted in chronic phase or accelerated phase; patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy with filgrastim (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMC) autologous or conventional HCT for advanced CML may be enrolled provided they are in CR or CP and have < 5% marrow blasts at time of transplant
  • Myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD)- Only patients with MDS/refractory anemia (RA) or MDS/refractory anemia with ringed sideroblasts (RARS) will be eligible for this protocol; additionally patients with myeloproliferative syndromes (MPS) will be eligible; those patients with MDS or MPS with > 5% marrow blasts (including those with transformation to AML) must receive cytotoxic chemotherapy and achieve < 5% marrow blasts at time of transplant
  • Renal cell carcinoma- Must have evidence of disease not amenable to surgical cure or history of or active metastatic disease by radiological and histologic criteria
  • DONOR: FHCRC matching allowed will be grade 1.0 to 2.1: Unrelated donors who are prospectively:
  • Matched for human leukocyte antigen (HLA)-A, B, C, major histocompatibility complex, class II, DR beta 1 (DRB1) and major histocompatibility complex, class II, DQ beta 1 (DQB1) by high resolution typing;
  • Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
  • DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
  • DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0201, and this type of mismatch is not allowed
  • DONOR: G-PBMC only will be permitted as a HSC source on this protocol

Who cannot join

  • Patients with rapidly progressive intermediate or high grade NHL
  • Renal cell carcinoma patients
  • With expected survival of less than 6 months
  • Disease resulting in severely limited performance status (< 70%)
  • Any vertebral instability
  • History of brain metastases
Show all 21Show fewer
  • Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant
  • Patients with non-hematological tumors except renal cell carcinoma
  • Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
  • Cardiac ejection fraction < 35%; ejection fraction is required if there is a history of anthracycline exposure or history of cardiac disease
  • Diffusing capacity of the lung for carbon monoxide (DLCO) < 40% and/or receiving supplementary continuous oxygen
  • The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules
  • Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease
  • Karnofsky scores < 60 (except renal cell carcinoma [RCC])
  • Patients with > grade II hypertension by Common Toxicity Criteria (CTC)
  • Human immunodeficiency virus (HIV) positive patients
  • The addition of cytotoxic agents for "cytoreduction" with the exception of hydroxyurea and imatinib mesylate will not be allowed within two weeks of the initiation of conditioning
  • DONOR: Marrow donors
  • DONOR: Donors who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of G-PBMC

Trial locations and contacts

10 sites in 3 countries.

10 sites in 3 countries

United States7 sites

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Rocky Mountain Cancer Centers-Midtown

    Denver, Colorado, 80218

  • Froedtert Memorial Lutheran Hospital, Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • Stanford University Hospitals and Clinics

    Stanford, California, 94305

Other trials in United States

Germany2 sites

  • Universitaet Leipzig

    Leipzig, D-04103

  • University of Tuebingen-Germany

    Tübingen, D-72076

Other trials in Germany

Italy1 site

  • University of Torino

    Torino, 10126

Other trials in Italy

About this study

Official title: Prolonged Mycophenolate Mofetil and Truncated Cyclosporine Postgrafting Immunosuppression to Reduce Life-Threatening GVHD After Unrelated Donor Peripheral Blood Cell Transplantation Using Nonmyeloablative Conditioning for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-Center Trial

This phase I/II trial studies whether stopping cyclosporine before mycophenolate mofetil is better at reducing the risk of life-threatening graft-versus-host disease (GVHD) than the previous approach where mycophenolate mofetil was stopped before cyclosporine. The other reason this study is being done because at the present time there are no curative therapies known outside of stem cell transplantation for these types of cancer. Because of age or underlying health status, patients may have a higher likelihood of experiencing harm from a conventional blood stem cell transplant. This study tests whether this new blood stem cell transplant method can be made safer by changing the order and length of time that immune suppressing drugs are given after transplant.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine whether the incidence of life-threatening GVHD can be reduced after unrelated donor peripheral blood mononuclear cell (PBMC) hematopoietic cell transplantation (HCT) using nonmyeloablative conditioning with earlier discontinuation of cyclosporine (CSP) and extended administration of mycophenolate mofetil (MMF) in patients with hematologic malignancies and metastatic renal cell carcinoma.

SECONDARY OBJECTIVES:

  1. To compare the incidence of acute and chronic GVHD to protocols 1463 and 1641.

II. To compare the utilization of corticosteroids to protocols 1463 and 1641.

III. To compare survival to that achieved under protocol 1463 and 1641.

OUTLINE:

CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2, and undergo total-body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic PBMC transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 80 with taper to day 150 and mycophenolate mofetil PO or IV thrice daily (TID) on days 0-30, BID on days 31-150, and then taper to day 180. Treatment continues in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 24 months and then yearly for 5 years.

Being tested
fludarabine phosphate, total-body irradiation, nonmyeloablative allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation, cyclosporine
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Leukemia, Myelomonocytic, Chronic

What participants receive

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

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • total-body irradiationRadiation

    Also called TBI

    Undergo TBI

  • nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo allogeneic PBMC transplantation

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo allogeneic PBMC transplantation

  • cyclosporineDrug

    Also called ciclosporin, cyclosporin, cyclosporin A, CYSP

    Given PO

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given PO or IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00078858
Study groupRoleWhat they receive
Treatment (prolonged MMF and truncated CSP)ExperimentalCONDITIONING: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, and undergo TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBMC transplant on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 80 with taper to day 150 and mycophenolate mofetil PO or IV TID on days 0-30, BID on days 31-150, and then taper to day 180. Treatment continues in the absence of unacceptable toxicity.
Receives: Drug: fludarabine phosphate; Radiation: total-body irradiation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Drug: cyclosporine; Drug: mycophenolate mofetil; Other: laboratory biomarker analysis

What is being measured

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

  1. Incidence of life-threatening GVHD in patients undergoing a modified taper of post-grafting immunosuppression after undergoing nonmyeloablative HSCT from matched unrelated donors

    Life-threatening GVHD defined as (1) death related to GVHD or its treatment, (2) disability caused by GVHD or its treatment (3) 3 or more major infections in a calendar year or (4) suicidal ideation because of GVHD.

    Measured: 1 year

Secondary outcomes (4)

  1. Need for corticosteroid treatment, defined as more than 1 mg/kg or equivalent of prednisone for more than 3 days at any time after transplant

    Measured: 1 year

  2. Graft rejection

    Measured: Up to day 365

  3. Incidence of acute and chronic GVHD

    Measured: Up to 7 years

  4. Overall survival

    Measured: Up to 7 years

Timeline

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

  1. First posted9 Mar 2004 (estimated)
  2. Study startSep 2003
  3. Primary 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00078858
Sponsor's protocol ID
1668.00
Other IDs
NCI-2012-00668, 1668.00, P30CA015704, P01CA018029
Status last verified
Feb 2019
First submitted
8 Mar 2004
Last updated
18 Jan 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.

    PubMed 32499241

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing fludarabine phosphate, total-body irradiation and nonmyeloablative allogeneic hematopoietic stem cell transplantation in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Center at 10 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 21 exclusion criteria. 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 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Germany, Italy. 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 combined 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.

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?

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?

Incidence of life-threatening GVHD in patients undergoing a modified taper of post-grafting immunosuppression after undergoing nonmyeloablative HSCT from matched unrelated donors (time frame: 1 year). 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 NCT00078858, 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 18 Jan 2020.

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