Active Chronic Graft Versus Host DiseasePhase 2NCT01001780
Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease
A Phase 2 study testing Pentostatin; Cyclophosphamide; Rituximab in people with Active Chronic Graft Versus Host Disease, run by University of Rochester at 1 site in United States.
Trial summary
Chronic graft-versus-host disease (GvHD) is a severe, life threatening complication from getting a bone marrow or stem cell transplant. It is caused by certain cells from the donor that attack your cells. The usual treatments, prednisone and cyclosporine, don't work very well in chronic GVHD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Active Chronic Graft Versus Host Disease
- What is being tested?
- Pentostatin; Cyclophosphamide; Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Jan 2011
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of chronic GvHD requires at least one diagnostic and/or at least one distinctive manifestation. The latter must be confirmed by pertinent biopsy, laboratory tests, or radiology in the same or another organ. (See 19.11 details)
- Confirmation of active chronic GvHD is desired but may not be feasible.
- Age >/= 18 yrs. No gender or ethnic restrictions.
- Previously untreated chronic GvHD
- Up to 15 days' of single agent therapy may be given for patients to be considered "previously-untreated", provided progression is not observed.
- Vogelsang score20 >/= 2
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- If patients progress while on prednisone >/= 0.5 mg/kg/day (or equivalent) for treatment of acute GvHD as they develop chronic GvHD, they may be considered candidates irrespective of the Vogelsang Score.
- Prior therapy. Patients must have received prednisone >/= 0.5 mg/kg/day plus one (or more) of the following second agents: tacrolimus, cyclosporine, sirolimus, or mycophenolate.
- All second and subsequent failures are eligible.
- Special circumstances: involvement of a "critical organ". In these cases, progressive involvement after the use of initial therapy will suffice as a eligibility criteria irrespective of the Vogelsang score.
Who cannot join
- Previous history of severe adverse reaction to either study agent.
- Prior exposure alone to any of the agents in PCR is not a contraindication, Use of more than one of the agents in PCR to treat GvHD will exclude patients from entry.
- Serious active infection (especially hepatitis B or C) not responding to therapy.
- Active malignancy and/or the requirement of immunomodulation as treatment of malignancy.
- Hematologic abnormalities: WBC <3.0 K/uL, ANC < 1.0 K/uL, Hgb < 8.0 g/dL, platelets < 50.0 K/uL.
- Non-hematologic toxicities*:
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- *Renal. Measured creatinine clearance <35 ml/min or the concomitant need for dialysis.
- *Pulmonary. DLCO <40%, FEV1, 50%.
- *Hepatic. LFT (as measured by AST, ALT, T.bili) One or all of the levels found to be >3 x normal.
- Other. History of any significant co-morbid disease felt to make proposed therapy excessively risky.
- Psychiatric. Patients with uncompensated severe psychiatric illness that would preclude signing the necessary consent forms or being compliant.
- Compliance. Patients unlikely to adhere to study procedure and/or is unable or unwilling to return for necessary follow-up.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Rochester Medical Center
Rochester, New York, 14642
About this study
Chronic graft-versus-host disease (GvHD) is a severe, life threatening complication from getting a bone marrow or stem cell transplant. It is caused by certain cells from the donor that attack your cells. The usual treatments, prednisone and cyclosporine, don't work very well in chronic GVHD.
This research is being done to determine if the combination of the chemotherapeutic and immunosuppressive, drugs pentostatin, cyclophosphamide and the monoclonal antibody rituximab, used as in the "PCR" combination will prove useful in the treatment of certain patients with chronic GvHD (namely those who are unlikely to respond to standard therapy).
Read the detailed description
As above, your chronic GvHD either has not responded to, or is not expected to, respond to standard immunosuppressive treatment for chronic GvHD. These standard treatments are given in relatively low doses over long intervals. Thus, in this study we are testing an alternate strategy, using a more intensive, combined therapy with the PCR combination to determine if it will improve outcomes. PENTOSTATIN, CYCLOPHOSPHAMIDE plus RITUXIMAB ("PCR") are FDA-approved drugs for chemotherapy of certain lymphomas/leukemias, and although each has been used separately to treat patients with chronic GvHD, they have not been approved as immunosuppressant for the treatment of chronic GvHD, either separately or together. We will study the "PCR" combination in 9-17 patients with chronic GvHD who are refractory to, or not expected to respond to standard therapy. Response will be measured by the achievement of a documented complete remission (i.e., full resolution of all symptoms and signs), and thus, a shortening of the total duration of immunosuppressive (anti-chronic GvHD) therapy. This latter effect may reduce overall infections.
- Conditions
- Active Chronic Graft Versus Host Disease
- Being tested
- Pentostatin; Cyclophosphamide; Rituximab
- Keywords
- Graft versus Host Disease, Allogeneic Hematopoietic Stem Cell Transplant
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pentostatin; Cyclophosphamide; RituximabDrug
Also called Pentostatin - Nipent, Cyclophosphamide - Cytoxan, Rituximab - Rituxan
Pentostatin 2mg/m2 IV day+1 (up to 6 cycles) Cyclophosphamide 600mg/m2 IV day+1 (up to 6 cycles) Rituximab 375mg/m2 IV day+1 (up to 6 cycles)
| Study group | Role | What they receive |
|---|---|---|
| Pentostatin, Cyclophosphamide, Rituximab | Experimental | Not described Receives: Drug: Pentostatin; Cyclophosphamide; Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine whether complete response rate following use of PCR regimen exceeds 25% in selected (for poor prognosis) chronic GvHD patients.
Measured: One year
Assess the ability to successfully wean patients from all immunosuppressive therapy following complete response.
Measured: One year
Secondary outcomes (4)
Describe the incidence, frequency and type of all observed opportunistic infections.
Measured: One year
Describe the pattern of immune recovery in these patients
Measured: One year
Assess the incidence, frequency and type of hematologic dysfunction before and after therapy.
Measured: One year
Assess the incidence of relapse (of the underlying malignant diagnosis for which the allogeneic hematopoietic stem cell transplant was performed), progression-free and overall survival.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2009 (estimated)
- Study startAug 2009
- Primary completionJan 2011
- Study completionJan 2011
Why it stopped: Study stopped early due to poor accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Active Chronic Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gordon Phillips, MD, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01001780
- Sponsor's protocol ID
- 25260
- Status last verified
- Oct 2013
- First submitted
- 26 Oct 2009
- Last updated
- 16 Oct 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT01001780
- Acronym / sponsor ID
- 25260
- Conditions
- Active Chronic Graft Versus Host Disease
- Keywords
- Graft versus Host Disease, Allogeneic Hematopoietic Stem Cell Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study stopped early due to poor accrual.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- Aug 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 27 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic graft-versus-host disease (GvHD) is a severe, life threatening complication from getting a bone marrow or stem cell transplant. It is caused by certain cells from the donor that attack your cells. The usual treatments, prednisone and cyclosporine, don't work very well in chronic GVHD.
This research is being done to determine if the combination of the chemotherapeutic and immunosuppressive, drugs pentostatin, cyclophosphamide and the monoclonal antibody rituximab, used as in the "PCR" combination will prove useful in the treatment of certain patients with chronic GvHD (namely those who are unlikely to respond to standard therapy).
Detailed description
As above, your chronic GvHD either has not responded to, or is not expected to, respond to standard immunosuppressive treatment for chronic GvHD. These standard treatments are given in relatively low doses over long intervals. Thus, in this study we are testing an alternate strategy, using a more intensive, combined therapy with the PCR combination to determine if it will improve outcomes. PENTOSTATIN, CYCLOPHOSPHAMIDE plus RITUXIMAB ("PCR") are FDA-approved drugs for chemotherapy of certain lymphomas/leukemias, and although each has been used separately to treat patients with chronic GvHD, they have not been approved as immunosuppressant for the treatment of chronic GvHD, either separately or together. We will study the "PCR" combination in 9-17 patients with chronic GvHD who are refractory to, or not expected to respond to standard therapy. Response will be measured by the achievement of a documented complete remission (i.e., full resolution of all symptoms and signs), and thus, a shortening of the total duration of immunosuppressive (anti-chronic GvHD) therapy. This latter effect may reduce overall infections.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pentostatin, Cyclophosphamide, Rituximab | Experimental | Drug: Pentostatin; Cyclophosphamide; Rituximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Diagnosis of chronic GvHD requires at least one diagnostic and/or at least one distinctive manifestation. The latter must be confirmed by pertinent biopsy, laboratory tests, or radiology in the same or another organ. (See 19.11 details)
- Confirmation of active chronic GvHD is desired but may not be feasible.
- Age >/= 18 yrs. No gender or ethnic restrictions.
- Previously untreated chronic GvHD
- Up to 15 days' of single agent therapy may be given for patients to be considered "previously-untreated", provided progression is not observed.
Key exclusion criteria (12 listed)
- Previous history of severe adverse reaction to either study agent.
- Prior exposure alone to any of the agents in PCR is not a contraindication, Use of more than one of the agents in PCR to treat GvHD will exclude patients from entry.
- Serious active infection (especially hepatitis B or C) not responding to therapy.
- Active malignancy and/or the requirement of immunomodulation as treatment of malignancy.
- Hematologic abnormalities: WBC <3.0 K/uL, ANC < 1.0 K/uL, Hgb < 8.0 g/dL, platelets < 50.0 K/uL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pentostatin; Cyclophosphamide; RituximabAlso: Pentostatin - Nipent, Cyclophosphamide - Cytoxan, Rituximab - RituxanPentostatin 2mg/m2 IV day+1 (up to 6 cycles) Cyclophosphamide 600mg/m2 IV day+1 (up to 6 cycles) Rituximab 375mg/m2 IV day+1 (up to 6 cycles) | Drug | Pentostatin, Cyclophosphamide, Rituximab |
Primary outcome
Determine whether complete response rate following use of PCR regimen exceeds 25% in selected (for poor prognosis) chronic GvHD patients.
Time frame: One year
Assess the ability to successfully wean patients from all immunosuppressive therapy following complete response.
Time frame: One year
4 secondary outcomes
Describe the incidence, frequency and type of all observed opportunistic infections.
Time frame: One year
Describe the pattern of immune recovery in these patients
Time frame: One year
Assess the incidence, frequency and type of hematologic dysfunction before and after therapy.
Time frame: One year
Assess the incidence of relapse (of the underlying malignant diagnosis for which the allogeneic hematopoietic stem cell transplant was performed), progression-free and overall survival.
Time frame: One year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gordon Phillips, MD principal investigator
University of Rochester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pentostatin; Cyclophosphamide; Rituximab in people with Active Chronic Graft Versus Host Disease, run by University of Rochester 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 10 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: withdrawn, as of the sponsor's last update on 16 Oct 2013. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Determine whether complete response rate following use of PCR regimen exceeds 25% in selected (for poor prognosis) chronic GvHD patients. (time frame: One year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Oct 2013.