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Leukemia, Mast-CellPhase 2NCT00186628

Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD

A Phase 2 study testing Total lymphoid irradiation, Rituximab and Anti-thymoglobulin, rabbit (ATG, rabbit ATG) in people with Leukemia, Mast-Cell and Mantle-cell Lymphoma, run by Stanford University 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

To determine if rituximab administered after allogeneic transplantation decreases the incidence of chronic graft-vs-host disease (cGvHD) Read more about this study

Who is it for?
Ages 18 to 76 years
Conditions the study is for
Leukemia, Mast-Cell, Mantle-cell Lymphoma
What is being tested?
Total lymphoid irradiation, Rituximab and Anti-thymoglobulin, rabbit (ATG, rabbit ATG)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
Jun 2005to Dec 2010
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 18 to 76 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Recipient Inclusion Criteria:

  • Between 18 and 76 years of age
  • Chronic lymphocytic leukemia (CLL):
  • Unmutated IgG VH gene status
  • Mutated IgG VH genes (> 2% nucleotide change compared to somatic sequence)
  • Complete remission benefit most from allogeneic hematopoietic stem cell transplant (HSCT). (Physicians will be encouraged to provide aggressive chemotherapy prior to nonmyeloablative transplantation.)
  • Mantle cell lymphoma (MCL): Transplant physicians believe subject would benefit from allogeneic HSCT.
  • Adequate renal (Cr < 2.4 mg/dL) and hepatic (Bilirubin < 3.0 mg/dL, Aspartate aminotransferase (AST) < 100 IU) function.
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
  • All subjects must provide written informed consent

Donor Inclusion Criteria:

  • Genotypically or phenotypically human leukocyte antigen (HLA)-identical.
  • Age < 76 unless cleared by institutional PI
  • Capable of giving written, informed consent.
  • Must consent to peripheral blood stem cell (PBSC) mobilization with G-CSF and apheresis

Recipient Exclusion Criteria:

  • Recipient has a 9 of 10 or 10 of 10 HLA identical donor (high resolution molecular genotyping at HLA A, B, C and DrB1, and DQ)
  • Pregnancy
  • Lactating
  • Serious uncontrolled infection
  • HIV seropositivity
  • Hepatitis B or C seropositivity
  • Cardiac function: ejection fraction < 40% or uncontrolled cardiac failure
  • Pulmonary: Diffusing capacity - carbon monoxide (DLCO) < 50% predicted
  • Liver function abnormalities: elevation of bilirubin to ≥ 3 mg/dL and/or AST > 100
  • Renal: creatinine > 2.4
  • Karnofsky performance score ≤ 60%
  • Patients with poorly controlled hypertension (systolic blood pressure > 150 or diastolic blood pressure > 90 repeatedly).
  • Known life-threatening hypersensitivity to rituximab or other anti-B cell antibodies.
  • Inability to comply with the allogeneic transplant treatment.
  • Uncontrolled central nervous system (CNS) involvement with disease

Donor Exclusion Criteria:

  • Identical twin to subject
  • Contra-indication to subcutaneous G-CSF at a dose of 16 mg/kg/d for 5 consecutive days
  • Serious medical or psychological illness
  • Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.
  • HIV seropositivity

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

Official title: An Open-label, Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of Chronic Graft Versus Host Disease After TLI/ARG Nonmyeloablative Allogeneic Stem Cell Transplantation

To determine if rituximab administered after allogeneic transplantation decreases the incidence of chronic graft-vs-host disease (cGvHD)

Read the detailed description

To test if prophylactic anti-B-cell therapy (weekly rituximab) given within 60 to 90 days after allogeneic transplantation will decrease allogeneic donor B-cell immunity and possibly the incidence of chronic graft-vs-host disease (cGvHD).

Being tested
Total lymphoid irradiation, Rituximab, Anti-thymoglobulin, rabbit (ATG, rabbit ATG), Cyclosporine, Mycophenylate mofetil
Medical subject headings
Leukemia, Mast-Cell, Lymphoma, Mantle-Cell

What participants receive

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

  • Total lymphoid irradiationProcedure or surgery

    Also called TLI

    Total lymphoid irradiation (TLI) administered at 80cGy for 10 days

  • RituximabDrug

    Also called Rituxan

    Rituximab 375 mg/m2 administered as an intravenous (IV) infusion once weekly for 4 doses.

  • Anti-thymoglobulin, rabbit (ATG, rabbit ATG)Drug

    Rabbit anti-thymoglobulin (ATG) administered from Day -11 through Day -7 (5 doses) at 1.5 mg/kg/day, for a total dose of 7.5 mg/kg.

  • CyclosporineDrug

    Also called CSP, Sandimmune

    Cyclosporine (CSP) administered orally at 6.25 mg/kg twice-a-day (BID) from Day -3 until through Day +56 post-peripheral blood progenitor cell (PBPC) infusion. Dose may be adjusted to maintain a therapeutic level of cyclosporine, or in response to renal insufficiency. If at Day +56, chimerism assessment demonstrates > 40% donor cells in the CD3+ lineage, and the patient is without evidence of GvHD, then cyclosporine taper will begin (6% reduction per week).

  • Mycophenylate mofetilDrug

    Also called MMF, CellCept

    Mycophenylate mofetil (MMF) will be administered at 15 mg/kg po Day 0, at 5 to 10 hours after mobilized PBPC infusion is complete

  • FilgrastimDrug

    Also called G-CSF, Granulocyte-colony stimulating factor, Neupogen

    Filgrastim provided as needed for neutrophil support

  • GranisetronDrug

    Also called Sancuso

    Granisetron administered as an anti-nausea agent (anti-emetic) at 1 mg orally 30 to 60 minutes before TLI

  • SolumedrolDrug

    Also called Medrol, Depo-Medrol, A-Methapred

    Solumedrol, an anti-inflammatory glucocorticoid containing methylprednisolone sodium succinate, administered at 1 mg/kg as a premedication for anti-thymoglobulin (ATG)

  • AcetaminophenDrug

    Also called Tylenol

    Acetaminophen administered orally at 650 mg 1 hour prior to infusion of PBPC

  • DiphenhydramineDrug

    Also called Benadryl

    Diphenhydramine administered by intravenous infusion at 50 mg 1 hour prior to infusion of PBPC

  • HydrocortisoneDrug

    Also called Westcort

    Hydrocortisone administered by intravenous infusion at 100 mg 1 hour prior to infusion of PBPC

Study groups in NCT00186628
Study groupRoleWhat they receive
Prophylactic RituximabExperimentalRituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
Receives: Procedure: Total lymphoid irradiation; Drug: Rituximab; Drug: Anti-thymoglobulin, rabbit (ATG, rabbit ATG); Drug: Cyclosporine; Drug: Mycophenylate mofetil; Drug: Filgrastim; Drug: Granisetron; Drug: Solumedrol; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Hydrocortisone

What is being measured

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

  1. Chronic Graft-vs-Host Disease (cGvHD)

    The cumulative percentage of participants who develop chronic graft-vs-host disease (cGvHD). Chronic cGvHD was defined as at least one instance of a clinically-accepted marker for cGvHD (see Filipovich, et al. Biology of Blood and Marrow Transplantation. 2005;11:945-955)

    Measured: 4 years

Secondary outcomes (3)

  1. Incidence of Relapse

    Subjects who Relapsed following after Allogeneic HSCT

    Measured: 4 years

  2. Mortality

    Number of participants who died within 100 days and within 1 year, non-relapse and associated with relapse.

    Measured: Day 100 and 1 year

  3. Overall Survival

    Measured: 4 years

Timeline

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

  1. First posted16 Sep 2005 (estimated)
  2. Study startJun 2005
  3. Primary completionNov 2010
  4. Study completionDec 2010

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
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00186628
Sponsor's protocol ID
IRB-02372
Other IDs
96160, BMT172, SPO, P01CA049605
Status last verified
Oct 2017
First submitted
14 Sep 2005
Last updated
28 Nov 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.

    PubMed 16338616

  • Arai S, Sahaf B, Narasimhan B, Chen GL, Jones CD, Lowsky R, Shizuru JA, Johnston LJ, Laport GG, Weng WK, Benjamin JE, Schaenman J, Brown J, Ramirez J, Zehnder JL, Negrin RS, Miklos DB. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012 Jun 21;119(25):6145-54. doi: 10.1182/blood-2011-12-395970. Epub 2012 May 4.

    PubMed 22563089

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Total lymphoid irradiation, Rituximab and Anti-thymoglobulin, rabbit (ATG, rabbit ATG) in people with Leukemia, Mast-Cell and Mantle-cell Lymphoma, run by Stanford University 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 28 Nov 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 28 Nov 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?

Chronic Graft-vs-Host Disease (cGvHD) (time frame: 4 years). 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 NCT00186628, which also lists 2 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 28 Nov 2017.

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