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

This study has been withdrawn prior to enrollment.
(Study stopped early due to poor accrual.)
Sponsor:
Information provided by (Responsible Party):
University of Rochester
ClinicalTrials.gov Identifier:
NCT01001780
First received: October 26, 2009
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Active Chronic Graft Versus Host Disease
Drug: Pentostatin; Cyclophosphamide; Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Determine whether complete response rate following use of PCR regimen exceeds 25% in selected (for poor prognosis) chronic GvHD patients. [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Assess the ability to successfully wean patients from all immunosuppressive therapy following complete response. [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Describe the incidence, frequency and type of all observed opportunistic infections. [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Describe the pattern of immune recovery in these patients [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Assess the incidence, frequency and type of hematologic dysfunction before and after therapy. [ Time Frame: One year ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: August 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01001780

Locations
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Investigators
Principal Investigator: Gordon Phillips, MD University of Rochester
  More Information

No publications provided

Responsible Party: University of Rochester
ClinicalTrials.gov Identifier: NCT01001780     History of Changes
Other Study ID Numbers: 25260
Study First Received: October 26, 2009
Last Updated: October 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Rochester:
Graft versus Host Disease
Allogeneic Hematopoietic Stem Cell Transplant

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Cyclophosphamide
Rituximab
Pentostatin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adenosine Deaminase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014