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Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease

Primary Purpose

Active Chronic Graft Versus Host Disease

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pentostatin; Cyclophosphamide; Rituximab
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Active Chronic Graft Versus Host Disease focused on measuring Graft versus Host Disease, Allogeneic Hematopoietic Stem Cell Transplant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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*:
  • *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.

Sites / Locations

  • University of Rochester Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pentostatin, Cyclophosphamide, Rituximab

Arm Description

Outcomes

Primary Outcome Measures

Determine whether complete response rate following use of PCR regimen exceeds 25% in selected (for poor prognosis) chronic GvHD patients.
Assess the ability to successfully wean patients from all immunosuppressive therapy following complete response.

Secondary Outcome Measures

Describe the incidence, frequency and type of all observed opportunistic infections.
Describe the pattern of immune recovery in these patients
Assess the incidence, frequency and type of hematologic dysfunction before and after therapy.
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.

Full Information

First Posted
October 26, 2009
Last Updated
October 14, 2013
Sponsor
University of Rochester
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1. Study Identification

Unique Protocol Identification Number
NCT01001780
Brief Title
Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease
Official Title
Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Withdrawn
Why Stopped
Study stopped early due to poor accrual.
Study Start Date
August 2009 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Rochester

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Active Chronic Graft Versus Host Disease
Keywords
Graft versus Host Disease, Allogeneic Hematopoietic Stem Cell Transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pentostatin, Cyclophosphamide, Rituximab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Pentostatin; Cyclophosphamide; Rituximab
Other Intervention Name(s)
Pentostatin - Nipent, Cyclophosphamide - Cytoxan, Rituximab - Rituxan
Intervention Description
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)
Primary Outcome Measure Information:
Title
Determine whether complete response rate following use of PCR regimen exceeds 25% in selected (for poor prognosis) chronic GvHD patients.
Time Frame
One year
Title
Assess the ability to successfully wean patients from all immunosuppressive therapy following complete response.
Time Frame
One year
Secondary Outcome Measure Information:
Title
Describe the incidence, frequency and type of all observed opportunistic infections.
Time Frame
One year
Title
Describe the pattern of immune recovery in these patients
Time Frame
One year
Title
Assess the incidence, frequency and type of hematologic dysfunction before and after therapy.
Time Frame
One year
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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. Exclusion Criteria: 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*: *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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gordon Phillips, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States

12. IPD Sharing Statement

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Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease

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