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Accelerated Phase Chronic Myelogenous LeukemiaPhase 2NCT00049504

Haploidentical Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer

A Phase 2 study testing cyclophosphamide, fludarabine phosphate and tacrolimus in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Center 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

This phase II trial studies how well giving fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil and total-body irradiation together with a donor bone marrow transplant works in treating patients with high-risk hematologic cancer. Read more about this study

Who is it for?
Any age
What is being tested?
cyclophosphamide, fludarabine phosphate and tacrolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteUnited States
Study dates
Jan 2002to Feb 2014
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Chronic myeloid leukemia (CML) in accelerated phase (AP)
  • Acute myeloid leukemia (AML) with high-risk cytogenetics [del(5q)/-5, del(7q)/-7, abnormal 3q, 9q, 11q, 20q, 21q, 17p, t(6:9), t(9;22), complex karyotypes (>= 3 abnormalities)] in complete remission (CR)1
  • AML >= CR2; patients should have < 5% marrow blasts at the time of transplant
  • High-risk ALL defined as: CR1 with high-risk cytogenetics; t(9;22), t(4;11), or hypodiploid (< 45 chromosomes) for pediatric patients; t(9;22), t(8;14), t(4;11), t(1;19) for adult patients; > 4 wk to achieve CR1; >= CR2 (patients should have < 5% marrow blasts at the time of transplant)
  • Myelodysplastic syndromes (MDS) (>int-1 per IPSS) after >= 1 prior cycle of induction chemotherapy; should have < 5% marrow blasts at the time of transplant
  • Multiple myeloma (MM) Stage II or III patients who have progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) or MM patients with refractory disease who may benefit from tandem autologous-nonmyeloablative allogeneic transplant
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  • Chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) or Hodgkin's Disease (HD) who are ineligible for autologous HSCT or who have resistant/refractory disease and who may benefit from tandem autologous nonmyeloablative allogeneic transplant
  • Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active graft-versus-host disease (GvHD) requiring immunosuppressive therapy
  • DONOR: Related donors who are identical for one HLA haplotype and mismatched at the HLA-A, -B, -C or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or -C allele mismatches

Who cannot join

  • Cross-match positive with donor
  • Patients with suitably matched related or unrelated donors
  • Patients with conventional transplant options (a conventional transplant should be the priority for eligible patients =< 50 yr of age who have a related donor mismatched for a single HLA-A, -B or DRB1 antigen)
  • Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
  • Presence of active, serious infection (e.g., mucormycosis, uncontrolled aspergillosis, tuberculosis)
  • Karnofsky Performance Status < 60 for adult patients
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  • Lansky-Play Performance Score < 60 for pediatric patients
  • Left ventricular ejection fraction < 35%
  • Diffusing capacity of the lung for carbon monoxide (DLCO) < 35% and/or receiving supplemental continuous oxygen
  • Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL or symptomatic biliary disease
  • Human immunodeficiency virus (HIV)-positive patients
  • Women of childbearing potential who are pregnant (beta-HCG+) or breast feeding
  • Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant
  • Life expectancy severely limited by diseases other than malignancy
  • DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the HVG direction
  • DONOR: Cross-match positive with recipient

Trial locations and contacts

1 site in 1 country.

United States1 site

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

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Nonmyeloablative Hematopoietic Stem Cell Transplantation for Patients With High-Risk Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Combined Immunosuppression Before and After Transplantation

This phase II trial studies how well giving fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil and total-body irradiation together with a donor bone marrow transplant works in treating patients with high-risk hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells by stopping them from dividing or killing them. Giving cyclophosphamide after transplant may also stop the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system 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

Read the detailed description

OBJECTIVES:

  1. To determine if engraftment can be achieved safely in patients with high-risk hematologic malignancies who undergo non-myeloablative bone marrow transplantation (BMT) from human leukocyte antigen (HLA)-haploidentical donors.

OUTLINE:

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total body irradiation on day -1.

TRANSPLANTATION: Patients undergo BMT, from an HLA-haploidentical donor, on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3.

GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV over 1-2 hours and then tacrolimus orally (PO), once tolerated, on days 4-180, with taper on day 86 in the absence of graft-versus-host disease. Patients also receive mycophenolate mofetil PO three times daily on days 4-35.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 months and then annually thereafter.

Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Burkitt Lymphoma, Hematologic Neoplasms, Intraocular Lymphoma

What participants receive

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

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • fludarabine phosphateDrug

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

    Given IV

  • tacrolimusDrug

    Also called FK 506, Prograf

    Given IV or orally

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given orally

  • polymerase chain reactionGenetic

    Also called PCR

    Correlative studies

  • fluorescence in situ hybridizationGenetic

    Also called fluorescence in situ hybridization (FISH)

    Correlative studies

  • polymorphism analysisGenetic

    Correlative studies

  • gene expression analysisGenetic

    Correlative studies

  • total-body irradiationRadiation

    Also called TBI

    Undergo total-body irradiation

  • allogeneic bone marrow transplantationProcedure or surgery

    Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

    Undergo haploidentical hematopoietic bone marrow transplantation

  • allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo haploidentical hematopoietic bone marrow transplantation

Study groups in NCT00049504
Study groupRoleWhat they receive
Treatment (nonmyeloablative HSCT)ExperimentalNONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total body irradiation on day -1. TRANSPLANTATION: Patients undergo BMT, from an HLA-haploidentical donor, on day 0. POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV over 1-2 hours and then tacrolimus PO, once tolerated, on days 4-180, with taper on day 86 in the absence of graft-versus-host disease. Patients also receive mycophenolate mofetil PO three times daily on days 4-35.
Receives: Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: tacrolimus; Drug: mycophenolate mofetil; Genetic: polymerase chain reaction; Genetic: fluorescence in situ hybridization; Genetic: polymorphism analysis; Genetic: gene expression analysis; Radiation: total-body irradiation; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation

What is being measured

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

  1. Donor Engraftment (Chimerism)

    Defined by the detection of at least 50% donor derived T-cells (CD3+), as a proportion of the total T-cell population

    Measured: At day +84 after transplantation

  2. Incidence of Grades III-IV Acute GVHD

    Grade III GVHD represents moderate severity. Grade IV GVHD represents extreme severity

    Measured: At any time within 200 days after transplantation

  3. Non-relapse-related Mortality

    Number of deaths without progression or recurrence of malignant disease

    Measured: Up to 200 days after transplantation

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startJan 2002
  3. Primary completionMar 2011
  4. Study completionFeb 2014

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00049504
Sponsor's protocol ID
1667.00
Other IDs
NCI-2010-00166
Status last verified
Apr 2017
First submitted
12 Nov 2002
Last updated
17 May 2017
Data monitoring committee
No
FDA-regulated device
No
Individual data sharing
No: Individual patient data is protected by HIPAA at each participant organization.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cyclophosphamide, fludarabine phosphate and tacrolimus in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Center 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?

The sponsor lists 9 inclusion and 16 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 17 May 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.

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 17 May 2017). 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?

Donor Engraftment (Chimerism) (time frame: At day +84 after transplantation). 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 NCT00049504.

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 May 2017.

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