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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01001780
Recruitment Status : Withdrawn (Study stopped early due to poor accrual.)
First Posted : October 27, 2009
Last Update Posted : October 16, 2013
Information provided by (Responsible Party):
University of Rochester

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).

Condition or disease Intervention/treatment Phase
Active Chronic Graft Versus Host Disease Drug: Pentostatin; Cyclophosphamide; Rituximab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease
Study Start Date : August 2009
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Arm Intervention/treatment
Experimental: Pentostatin, Cyclophosphamide, Rituximab Drug: Pentostatin; Cyclophosphamide; Rituximab
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)
Other Names:
  • Pentostatin - Nipent
  • Cyclophosphamide - Cytoxan
  • Rituximab - Rituxan

Primary Outcome Measures :
  1. Determine whether complete response rate following use of PCR regimen exceeds 25% in selected (for poor prognosis) chronic GvHD patients. [ Time Frame: One year ]
  2. Assess the ability to successfully wean patients from all immunosuppressive therapy following complete response. [ Time Frame: One year ]

Secondary Outcome Measures :
  1. Describe the incidence, frequency and type of all observed opportunistic infections. [ Time Frame: One year ]
  2. Describe the pattern of immune recovery in these patients [ Time Frame: One year ]
  3. Assess the incidence, frequency and type of hematologic dysfunction before and after therapy. [ Time Frame: One year ]
  4. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01001780

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United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
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Principal Investigator: Gordon Phillips, MD University of Rochester
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Responsible Party: University of Rochester Identifier: NCT01001780    
Other Study ID Numbers: 25260
First Posted: October 27, 2009    Key Record Dates
Last Update Posted: October 16, 2013
Last Verified: October 2013
Keywords provided by University of Rochester:
Graft versus Host Disease
Allogeneic Hematopoietic Stem Cell Transplant
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Adenosine Deaminase Inhibitors
Enzyme Inhibitors