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Chronic Myeloproliferative DisordersPhase 2NCT00589563

Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer

A Phase 2 study testing anti-thymocyte globulin, cyclophosphamide and etoposide in people with Chronic Myeloproliferative Disorders and Graft Versus Host Disease, run by City of Hope Medical Center at 2 sites in United States.

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

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral 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 2 years and older
What is being tested?
anti-thymocyte globulin, cyclophosphamide and etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
2 sitesUnited States
Study dates
May 2007to Feb 2012
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 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

DISEASE CHARACTERISTICS:

  • Diagnosis of hematological malignancy including any of the following:
  • Non-Hodgkin lymphoma (NHL) in any complete remission (CR) or partial response (PR)
  • Hodgkin lymphoma in any CR or PR
  • Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in any CR
  • Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood absolute blast count < 500/µL on the day of initiation of conditioning for patients with non-CR AML or ALL
  • Myelodysplastic syndromes (MDS) treated or untreated
  • Chronic myelogenous leukemia (CML) in chronic or accelerated phase
  • Multiple myeloma in any CR or PR
  • Chronic lymphocytic leukemia in CR or PR 2 or greater
  • Myelofibrosis and other myeloproliferative disorders
  • Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood absolute blast count < 500/µL on the day of initiation
  • High-risk disease defined as AML or ALL > CR1, accelerated phase CML, recurrent aggressive lymphoma, or active lymphoproliferative disease at transplant
  • Low-risk disease defined as AML or ALL in CR1, chronic phase CML, or low-grade lymphoproliferative disorder with controlled disease at transplant
  • Must be planning to receive 1 of the following conditioning regimens at City of Hope:
  • Fludarabine phosphate and melphalan for patients with hematological malignancies and contraindications for conventional myeloablative regimens due to age, co-morbidity, or previous transplant
  • Fractionated total-body irradiation (FTBI) and etoposide for patients with AML and ALL or CML in accelerated phase
  • FTBI and cyclophosphamide for patients with NHL, AML, CML, and MDS
  • Suitable unrelated donor available
  • HLA-matched or mismatched
  • Peripheral blood stem cells available
  • No bone marrow or ex vivo-engineered or processed graft (e.g., CD34-positive, T-cell depletion)
  • No uncontrolled CNS disease

PATIENT CHARACTERISTICS:

  • Karnofsky performance status (PS) 70-100% or ECOG PS 0-2
  • Creatinine < 1.3 mg/dL or creatinine clearance ≥ 70 mL/min
  • Ejection fraction > 45%
  • Direct bilirubin < 3 times upper limit of normal (ULN)
  • ALT and AST < 3 times ULN
  • Forced vital capacity, FEV1, and DLCO > 45% of predicted
  • Able to cooperate with oral medication intake
  • No active donor or recipient serology positive for HIV
  • No known contraindication to administration of sirolimus, tacrolimus, or anti-thymocyte globulin
  • No active hepatitis B or C
  • Negative pregnancy test

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Concurrent participation in other clinical trials for prevention or treatment of viral, bacterial, or fungal disease allowed provided agents do not interact with agents used in the current study

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

  • Banner Good Samaritan Medical Center

    Phoenix, Arizona, 85006

Other trials in United States

About this study

Official title: A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin, as Graft-versus-Host Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral 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 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, sirolimus, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .

Read the detailed description

OBJECTIVES:

Primary

  • To determine the incidence and severity of acute- and chronic-graft-versus-host disease (GVHD) after HLA-matched or -mismatched unrelated donor hematopoietic peripheral blood transplantation in patients with hematologic malignancies scheduled to receive immunosuppressive combination of sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD prophylaxis.
  • To determine the safety of this combination in the first six months post-transplant.

Secondary

  • To determine the time-to-engraftment, non-relapse mortality rate, overall and disease-free survival, incidence of disease relapse, and incidence of opportunistic infections with this GVHD prophylaxis.

OUTLINE: Patients are stratified according to conditioning regimen (fludarabine phosphate and melphalan vs fractionated total-body irradiation [FTBI] and etoposide vs FTBI and cyclophosphamide) and degree of donor/recipient HLA mismatch (high-risk vs low-risk).

  • Conditioning regimen: Patients receive 1 of 3 standard conditioning regimens beginning on day -9 or -8 and continuing to day -1 or 0.
  • Peripheral blood stem cell transplantation: Patients receive HLA-matched or mismatched unrelated donor peripheral blood stem cells on day 0.
  • Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously beginning on day -3 and then orally when tolerated, oral sirolimus on days -3 and -2, anti-thymocyte globulin IV over 4-8 hours on days -3 to 0, and methotrexate* IV on days 1, 3, and 6. Tacrolimus and sirolimus continue for 3-6 months (with taper).

NOTE: *Only patients with high-risk HLA mismatch receive treatment with methotrexate.

After completion of study therapy, patients are followed periodically for up to 2 years.

Being tested
anti-thymocyte globulin, cyclophosphamide, etoposide, fludarabine phosphate, melphalan
Keywords
graft versus host disease, infection, adult favorable prognosis Hodgkin lymphoma, adult unfavorable prognosis Hodgkin lymphoma, childhood favorable prognosis Hodgkin lymphoma, childhood unfavorable prognosis Hodgkin lymphoma, cutaneous B-cell non-Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage I adult Hodgkin lymphoma, stage I childhood Hodgkin lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II adult Hodgkin lymphoma, stage II childhood Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV adult Hodgkin lymphoma
Medical subject headings
Myeloproliferative Disorders, Graft vs Host Disease, Infections, 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

    0.5 mg/kg on day -3, 1.5 mg/kg on day -2 and 2.5 mg/kg on day -1 or day 0 from stem cell transplant

  • cyclophosphamideDrug

    60mg/kg on days -5 and -4 from stem cell transplant

  • etoposideDrug

    60mg/kg on day -4 from stem cell transplant

  • fludarabine phosphateDrug

    Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant

  • melphalanDrug

    Melphalan 140 mg/m2 on day -4 from stem cell transplant

  • methotrexateDrug

    For high risk HLA-mismatch transplant only: 5 mg/m2 on days +1, +3 and +6 from stem cell transplant

  • sirolimusDrug

    Adults: 12 mg loading dose on day -3 from stem cell transplant followed by 4 mg orally single morning daily dose.

    Pediatric Patients <40kg: 3 mg/m2 orally on day -3 from stem cell transplant followed by 1 mg/m2 orally single morning daily dose

  • tacrolimusDrug

    0.02 mg/kd/d CIV beginning on day -3 from stem cell transplant

  • allogeneic hematopoietic stem cell transplantationProcedure or surgery

    The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight

  • hematopoietic stem cell transplantationProcedure or surgery

    The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight

  • nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant, Melphalan 140 mg/m2 on day -4 from stem cell transplant

  • peripheral blood stem cell transplantationProcedure or surgery

    The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight

  • total-body irradiationRadiation

    1320 cGy in 11 fractions from day -8 to day -5 or day -9 to day -6 prior to stem cell transplant

Study groups in NCT00589563
Study groupRoleWhat they receive
Fludarabine/Melphalan ConditioningExperimentalFludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis
Receives: Biological: anti-thymocyte globulin; Drug: fludarabine phosphate; Drug: melphalan; Drug: methotrexate; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: hematopoietic stem cell transplantation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation
FTBI/Cytoxan ConditioningExperimentalFTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis
Receives: Biological: anti-thymocyte globulin; Drug: cyclophosphamide; Drug: methotrexate; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: hematopoietic stem cell transplantation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation
FTBI/Etoposide ConditioningExperimentalFTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis
Receives: Biological: anti-thymocyte globulin; Drug: etoposide; Drug: methotrexate; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: hematopoietic stem cell transplantation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation

What is being measured

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

  1. Cumulative Incidence of Grade II-IV Acute Graft-Versus-Host Disease (GVHD) at Day 100

    Patients were evaluated for the development of acute GVHD within the first 100 days post HSCT. The cumulative incidence of grade II-IV acute GVHD was determined using competing risk analysis. Competing risks for acute GVHD were death and nonengraftment.

    Measured: 100 Days Post Hematopoietic Stem Cell Transplant (HSCT)

  2. Severity of Acute GVHD

    All patients were considered for the evaluation of the severity of acute GVHD.

    Measured: 100 Days Post HSCT

  3. Cumulative Incidence of Chronic GVHD

    Patients were evaluated for the development of chronic GVHD from 101 days post HSCT to last contact or documented evidence of the disease. The cumulative incidence of chronic GVHD was determined using competing risk analysis. Competing risks for GVHD were death and nonengraftment.

    Measured: 2 year point estimate was provided.

  4. Severity of Chronic GVHD

    All Patients were considered for the evaluation of chronic GVHD severity.

    Measured: Patients were evaluated until they developed chronic GVHD, a median of 130 days post HSCT

Secondary outcomes (10)

  1. Time to Absolute Neutrophil Count Recovery (Engraftment)

    Absolute neutrophil count (ANC) recovery is defined as an ANC of ≥ 0.5 x 10^9/L (500/mm3) for three consecutive laboratory values obtained on different days

    Measured: Patients were evaluated until neutrophil recovery, a median of 15 days post HSCT

  2. Time to Platelet Count Recovery (Engraftment)

    Platelet recovery is defined as the first date of three consecutive laboratory values ≥ 25 x 10^9 L obtained on different days.

    Measured: Patients were evaluated until platelet recovery, a median of 14 days

  3. Occurence of Infections Including Cytomegalovirus and Epstein-Barr Virus Reactivation

    Participants were monitored throughout the trial (median of 28 months) for various infections/complications.

    Measured: Median Follow Up: 28 months (Range: 1-49 months)

  4. Occurrence of Thrombotic Microangiopathy

    Participants were monitored throughout the trial (median of 28 months) for various infections/complications. This is the number of participants who developed TMA.

    Measured: Median Follow Up: 28 Months (Range: 1-49 months)

  5. Occurence of Sinusoidal Obstructive Syndrome (SOS)

    Participants were monitored throughout the trial (median of 28 months) for various infections/complications. This is the number of participants who developed SOS.

    Measured: Median Follow Up: 28 Months (Range: 1-49 Months)

  6. Non-relapse Mortality at 100 Days Post HSCT

    Patients were evaluated for non-relapse mortality (NRM) throughout the study. Non-relapse mortality was considered any death not attributable to relapse or disease progression. The cumulative incidence of NRM was determined using competing risk analysis. Competing risks for NRM were death due to disease progression, relapse and nonengraftment.

    Measured: 100 day point estimate was provided

  7. Non-relapse Mortality at Two Years Post HSCT

    Patients were evaluated for non-relapse mortality (NRM) throughout the study. Non-relapse mortality was considered any death not attributable to relapse or disease progression. The cumulative incidence of NRM was determined using competing risk analysis. Competing risks for NRM were death due to disease progression, relapse and nonengraftment.

    Measured: 2 year point estimate was provided.

  8. Overall Survival at Two Years Post HSCT

    Patients were evaluated for survival (OS) throughout the study. Kaplan Meier estiamtes were calculated for overall survival using time from HSCT to death of any cause or for surviving patients last contact date.

    Measured: 2 year point estimate was provided.

  9. Event Free Survival at Two Years Post HSCT

    Patients were evaluated for event free survival (EFS) throughout the study. Events were defined as death, relapse, progression, or nonengraftment. Kaplan Meier estimates were calculated as time from HSCT to event.

    Measured: 2 year point estimate was provided.

  10. Incidence of Disease Relapse/Progression at 2 Years Post HSCT

    Patients were evaluated for relapse/progression post transplant throughout the study. The cumulative incidence of relapse/progression was determined using competing risk analysis. Competing risks for relapse were non-relapse mortality and nonengraftment.

    Measured: 2 year point estimate was provided.

Timeline

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

  1. First posted9 Jan 2008 (estimated)
  2. Study startMay 2007
  3. Primary completionFeb 2012
  4. Study completionFeb 2012

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
Supportive care
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00589563
Sponsor's protocol ID
06141
Other IDs
P30CA033572, CHNMC-06141, CDR0000579340
Status last verified
Sep 2014
First submitted
21 Dec 2007
Last updated
10 Sep 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing anti-thymocyte globulin, cyclophosphamide and etoposide in people with Chronic Myeloproliferative Disorders and Graft Versus Host Disease, run by City of Hope Medical Center at 2 sites 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 10 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 Aug 2014). 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?

Cumulative Incidence of Grade II-IV Acute Graft-Versus-Host Disease (GVHD) at Day 100 (time frame: 100 Days Post Hematopoietic Stem Cell Transplant (HSCT)). The study lists 4 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 NCT00589563.

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 10 Sep 2014.

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