Active Chronic Graft Versus Host Disease Clinical Trial
Official title:
Pentostatin, Cyclophosphamide Plus Rituximab (PCR) for the Therapy of Poor-Prognosis Chronic Graft-Versus-Host Disease
| Verified date | October 2013 |
| Source | University of Rochester |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Institutional Review Board |
| Study type | Interventional |
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).
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | January 2011 |
| Est. primary completion date | January 2011 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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. |
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | University of Rochester Medical Center | Rochester | New York |
| Lead Sponsor | Collaborator |
|---|---|
| University of Rochester |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Determine whether complete response rate following use of PCR regimen exceeds 25% in selected (for poor prognosis) chronic GvHD patients. | One year | No | |
| Primary | Assess the ability to successfully wean patients from all immunosuppressive therapy following complete response. | One year | No | |
| Secondary | Describe the incidence, frequency and type of all observed opportunistic infections. | One year | No | |
| Secondary | Describe the pattern of immune recovery in these patients | One year | No | |
| Secondary | Assess the incidence, frequency and type of hematologic dysfunction before and after therapy. | One year | No | |
| Secondary | 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. | One year | No |