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Kidney CancerPhase 2NCT00303719

Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy

A Phase 2 study testing anti-thymocyte globulin, cyclophosphamide and cyclosporine in people with Kidney Cancer and Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Read more about this study

Who is it for?
Ages Up to 75 years
Conditions the study is for
Kidney Cancer, Leukemia, Lymphoma
What is being tested?
anti-thymocyte globulin, cyclophosphamide and cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
342 participants
Where
1 siteUnited States
Study dates
26 Mar 2002to 8 May 2019
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 Up to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Standard patients will be enrolled into Arms 1-6. High risk patients (transplant with aplasia) will be considered separately in Arm 7.
  • Age and Graft criteria (all patients)
  • Patient's < or = 75 years old with a 5/6 or 6/6 related donor match are eligible.
  • Patient's < or = 75 years who have a 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated volunteer marrow and/or peripheral blood stem cell (PBSC) donor match are eligible.
  • Disease Criteria (standard risk patients)
  • Acute myelogenous leukemia
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  • Acute lymphocytic leukemia
  • Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible).
  • Non-Hodgkins lymphoma (NHL), Hodgkins, chronic lymphocytic leukemia, multiple myeloma demonstrating chemosensitive disease
  • Acquired bone marrow failure syndromes
  • Myelodysplastic syndrome of all subtypes including refractory anemia (RA) or all IPSS categories if severe pancytopenia, transfusion requirements not responsive to therapy, or high risk cytogenetics. Blasts must be less than 5%. If >5% requires therapy (induction or Hypomethylating agents) pre-transplant to decrease disease burden.
  • Renal cell cancer,
  • Chronic myeloproliferative disorder, i.e. myelofibrosis
  • Disease Criteria (High risk patients on Arm 7)
  • Patients with refractory leukemia or MDS may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody. These high risk patients will be analyzed separately in Arm 7.
  • Adequate organ function and performance status (all patients)

Who cannot join

  • Pregnancy or breast feeding
  • Evidence of HIV infection or known HIV positive serology
  • Active serious infection
  • Congenital bone marrow failure syndrome
  • Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI)
  • Chronic myelogenous leukemia (CML) in refractory blast crisis
Show all 12Show fewer
  • Intermediate or high grade NHL, mantle cell NHL, and Hodgkins disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
  • Multiple Myeloma progressive on salvage chemotherapy.
  • DONOR ELIGIBILITY
  • Related will undergo apheresis - if donor is unable to undergo apheresis, a bone marrow harvest is acceptable; unrelated volunteer donors must be able to undergo bone marrow harvest or apheresis.
  • All donors must be able to give informed consent.
  • Donors weighing less than 40 kg (children) will need evaluation by a pediatrician for suitability of the apheresis procedure. Informed consent must be obtained from parent or guardian as applicable for minors.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide and fludarabine together with total-body irradiation followed by cyclosporine and mycophenolate mofetil before the transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor stem cell transplant for hematologic cancer, metastatic breast cancer, or kidney cancer.

Read the detailed description

OBJECTIVES:

  • Determine if a nonmyeloablative regimen comprising cyclophosphamide, fludarabine, and radiotherapy followed by cyclosporine and mycophenolate mofetil provides a prompt and durable donor engraftment in patients with hematologic malignancies or kidney cancer who are undergoing allogeneic stem cell transplantation.
  • Determine the safety of this nonmyeloablative transplantation regimen in these patients.
  • Determine the risk of graft-versus-host-disease in patients treated with this regimen.
  • Determine the antineoplastic potency of nonmyeloablative stem cell transplantation in patients treated with this regimen.
  • Determine the effect of lower doses of daily fludarabine on treatment-related mortality (TRM) OUTLINE: Patients are stratified according to risk (standard vs high).
  • Preparative regimen*: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients undergo total body irradiation on day -1. Some patients also receive anti-thymocyte globulin (ATG)** IV every 12 hours on days -6 to -4. Patients who receive ATG* include the following:
  • Related donor recipients who have not received combination chemotherapy within the past 6 months
  • Unrelated donor recipients who have not received combination chemotherapy within the past 3 months
  • Unrelated donor recipients who have received only 1 induction course for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or blastic phase chronic myelogenous leukemia (CML) NOTE: **Patients who underwent prior autologous stem cell transplantation in the past year do not receive ATG.
  • Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0.
  • Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV over 2 hours beginning on day -3 and continuing until at least day 100. Patients also receive mycophenolate mofetil IV or orally twice daily on days -3 to 30.
  • Donor lymphocyte infusion (DLI): Patients without active GVHD but deteriorating donor chimerism may receive DLI IV over 2 hours.

After completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.

Being tested
anti-thymocyte globulin, cyclophosphamide, cyclosporine, fludarabine, mycophenolate mofetil
Keywords
leukemia, lymphoma, myeloma
Medical subject headings
Kidney Neoplasms, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes

What participants receive

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

  • anti-thymocyte globulinBiological

    Also called ATG

    ATG dose is 15 mg/kg intravenous (IV) every 12 hours for 6 doses on days -6, -5, and -4.

    Those that should/will receive ATG in the preparative regimen:

    • Related donor recipients who have not had exposure to combination chemotherapy in the 6 months preceding transplant should
    • Unrelated donor recipients who have not had exposure to combination chemotherapy in the 3 months preceding transplant will
    • Unrelated donor recipients who have had only a single induction cycle for the treatment of ALL/AML or MDS or CML blast crisis should
    • Recipients with a prior autologous transplant in the year prior to second transplant do not require ATG.

  • cyclophosphamideDrug

    Also called Cytoxan

    Cyclophosphamide will be given in a two hour infusion, total dose 50 mg/kg on day -6.

  • cyclosporineDrug

    Also called CSA

    Patients will receive cyclosporine A (CSA) therapy beginning on day -3 maintaining a level of >200. For adults the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. For children < 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours. Patients will receive CSA until day +100.

  • fludarabineDrug

    Also called Fludara

    Fludarabine 30 mg/m^2/day intravenous (IV) on day -6 through day -2., total dose 150 mg/m^2 for 5 days.

  • mycophenolate mofetilDrug

    Also called MMF

    Mycophenolate mofetil (MMF) 1.5 gram twice a day (BID) or if < 50 kg will be given 15 mg/kg orally(po) BID,beginning on day -3, and discontinue at day +30 or 7 days after engraftment (3 consecutive days of absolute neutrophil count (ANC) > 0.5 x 109 /L).

  • stem cell transplantationProcedure or surgery

    Also called peripheral blood stem cell transplantation, bone marrow transplant

    On day 0, if related donor, stem cells are infused via central line. If unrelated donor, marrow/PBSC is infused after arrival and processing on day 0.

  • total body irradiationRadiation

    Also called TBI

    The dose of TBI will be 200 cGy given in a single fraction on day -1.

  • filgrastimDrug

    Also called G-CSF

    Patients with white blood cell (WBC) counts < 2500 any time after stem cell infusion will be started on G-CSF support at Day +5 at a dose of 5 mcg/kg intravenously or subcutaneously (IV/SQ) daily rounded to vial size until absolute neutrophil count (ANC) > 2500 for 2 consecutive days.

Study groups in NCT00303719
Study groupRoleWhat they receive
High Risk PatientsExperimentalNonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.
Receives: Biological: anti-thymocyte globulin; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine; Drug: mycophenolate mofetil; Procedure: stem cell transplantation; Radiation: total body irradiation; Drug: filgrastim
Standard Risk PatientsExperimentalNonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.
Receives: Biological: anti-thymocyte globulin; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine; Drug: mycophenolate mofetil; Procedure: stem cell transplantation; Radiation: total body irradiation; Drug: filgrastim

What is being measured

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

  1. Neutrophil and Donor Cell Engraftment

    Successful sustained engraftment is defined as primary neutrophil engraftment by day 42 and e90% donor cells at day 100, with or without DLI.

    Engraftment based on absolute neutrophil count of donor origin > 0.5 x 10e9 /L for 3 days by day 42

    Measured: Day 42 and Day 100

Secondary outcomes (4)

  1. Serious Adverse Events

    Safety by development of severe adverse events within 100 days of transplant

    Measured: Day 100

  2. Transplant Related Mortality

    > 30% transplant related mortality at 100 days (non-relapse).

    Measured: Day 100

  3. Overall Survival

    Measured: 1 year

  4. Acute Graft-Versus-Host Disease

    Grade III-IV graft versus host disease

    Measured: Day 100

Timeline

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

  1. First posted17 Mar 2006 (estimated)
  2. Study start26 Mar 2002
  3. Primary completion8 May 2019
  4. Study completion8 May 2019

Why it stopped: IRB Study Closure

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
342 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00303719
Sponsor's protocol ID
2001LS058
Other IDs
UMN-MT2001-10, 0108M06725
Status last verified
Apr 2020
First submitted
15 Mar 2006
Last updated
12 May 2020
Data monitoring committee
Yes

Publications

  • Warlick E, Ahn KW, Pedersen TL, Artz A, de Lima M, Pulsipher M, Akpek G, Aljurf M, Cahn JY, Cairo M, Chen YB, Cooper B, Deol A, Giralt S, Gupta V, Khoury HJ, Kohrt H, Lazarus HM, Lewis I, Olsson R, Pidala J, Savani BN, Seftel M, Socie G, Tallman M, Ustun C, Vij R, Vindelov L, Weisdorf D. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era. Blood. 2012 Apr 26;119(17):4083-90. doi: 10.1182/blood-2012-02-409763. Epub 2012 Mar 9.

    PubMed 22408257

  • Warlick ED, DeFor TE, Bejanyan N, Holtan S, MacMillan M, Blazar BR, Dusenbery K, Arora M, Bachanova V, Cooley S, Lazaryan A, McGlave P, Miller JS, Rashidi A, Slungaard A, Vercellotti G, Ustun C, Brunsein C, Weisdorf D. Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up. Biol Blood Marrow Transplant. 2019 Jan;25(1):56-62. doi: 10.1016/j.bbmt.2018.07.038. Epub 2018 Aug 1.

    PubMed 30077015

  • Bachanova V, Burke MJ, Yohe S, Cao Q, Sandhu K, Singleton TP, Brunstein CG, Wagner JE, Verneris MR, Weisdorf DJ. Unrelated cord blood transplantation in adult and pediatric acute lymphoblastic leukemia: effect of minimal residual disease on relapse and survival. Biol Blood Marrow Transplant. 2012 Jun;18(6):963-8. doi: 10.1016/j.bbmt.2012.02.012. Epub 2012 Mar 16.

    PubMed 22430088

  • Bachanova V, Sandhu K, Yohe S, Cao Q, Burke MJ, Verneris MR, Weisdorf D. Allogeneic hematopoietic stem cell transplantation overcomes the adverse prognostic impact of CD20 expression in acute lymphoblastic leukemia. Blood. 2011 May 12;117(19):5261-3. doi: 10.1182/blood-2011-01-329573. Epub 2011 Mar 14.

    PubMed 21403127

  • Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Blood. 2009 Mar 26;113(13):2902-5. doi: 10.1182/blood-2008-10-184093. Epub 2009 Jan 28.

    PubMed 19179301

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing anti-thymocyte globulin, cyclophosphamide and cyclosporine in people with Kidney Cancer 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?

The sponsor lists 16 inclusion and 12 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: stopped early, as of the sponsor's last update on 12 May 2020. 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 12 May 2020). 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?

Neutrophil and Donor Cell Engraftment (time frame: Day 42 and Day 100). 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 NCT00303719, which also lists 5 linked publications.

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 12 May 2020.

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