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

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ClinicalTrials.gov Identifier: NCT01001780
Recruitment Status : Withdrawn (Study stopped early due to poor accrual.)
First Posted : October 27, 2009
Last Update Posted : October 16, 2013
Sponsor:
Information provided by (Responsible Party):
University of Rochester

Tracking Information
First Submitted Date  ICMJE October 26, 2009
First Posted Date  ICMJE October 27, 2009
Last Update Posted Date October 16, 2013
Study Start Date  ICMJE August 2009
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 26, 2009)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2009)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease
Official Title  ICMJE Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Active Chronic Graft Versus Host Disease
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Pentostatin, Cyclophosphamide, Rituximab
Intervention: Drug: Pentostatin; Cyclophosphamide; Rituximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 14, 2013)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 26, 2009)
17
Actual Study Completion Date  ICMJE January 2011
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01001780
Other Study ID Numbers  ICMJE 25260
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Rochester
Study Sponsor  ICMJE University of Rochester
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gordon Phillips, MD University of Rochester
PRS Account University of Rochester
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP