A Randomized Phase II Study to Determine the Most Promising Postgrafting Immunosuppression for Prevention of Acute GVHD after Unrelated Donor G-CSF mobilized Peripheral Blood Mononuclear Cell (G-PBMC) Transplantation using Nonmyeloablative Conditioning for Patients with Hematologic Malignancies. A Multi-Center Trial. - 1938.00

• Conditions: Hematologic malignancies

• Registration Number: EUCTR2005-003305-90-DE
• Lead Sponsor: Fred Hutchinson Cancer Research Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-10-17
• Last Update Posted: 2 February 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Ages >50 years with hematologic malignancies treatable by unrelated HCT.

2. Ages <= 50 years of age with hematologic diseases treatable by allogeneic HCT who through pre-existing medical conditions or prior therapy are considered to be at high risk for regimen related toxicity associated with a conventional transplant (>40% risk of TRM). This criterion can include patients with Charleson comorbidity index (CCI) score >139 (see Appendix Q). Transplants should be approved for these inclusion criteria by both the participating institutions’ patient review committees such as the Patient Care Conference (PCC) at the FHCRC and by the principal investigators at the collaborating centers. Patients £ 50 years of age who have received previous high-dose transplantation do not require patient review committee approvals. All children < 12 years must be discussed with the FHCRC PI (Michael Maris, MD 206-667-2480) prior to registration.

3. Ages <= 50 years of age with chronic lymphocytic leukemia (CLL) (these patients do not require patient review committee approvals).

4. Ages <= 50 years of age with hematologic diseases treatable by allogeneic HCT who refuse a conventional HCT. Transplants must be approved for these inclusion criteria by both the participating institutions’ patient review committee such as PCC at the FHCRC and by the principal investigators at the collaborating centers.
5. The following diseases will be permitted although other diagnoses can be considered if approved by PCC or the participating institutions’ patient review committees and the principal investigators.
· Aggressive nonHodgkin lymphomas (NHL) and Other Histologies Such as Diffuse large B cell NHL– not eligible for autologous HSCT, not eligible for conventional myeloablative HSCT, or after failed autologous HSCT.
· Mantle Cell NHL -may be treated in first CR.
· Low grade NHL– with < 6 month duration of CR between courses of conventional therapy
· CLL – Must be refractory to fludarabine or fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-CDA, pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog).
· Hodgkin Disease – must have received and failed frontline therapy.
· Multiple Myeloma – must have received prior chemotherapy. Consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted.
· Acute Myeloid Leukemia (AML)– must have < 5% marrow blasts at the time of transplant.
· Acute Lymphocytic Leukemia (ALL) – must have <5% marrow blasts at the time of transplant.
· Chronic Myeloid Leukemia (CML) – Patients will be accepted in chronic phase or accelerated phase. Patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy with G-PBMC autologous or conventional HCT for advanced CML may be enrolled provided they are in CR or CP and have <5% marrow blasts at time of transplant
· Myelodysplasia(MDS)/Myeloproliferative Syndrome (MPS) – Only patients with MDS/RA or MDS/RARS will be eligible for this protocol. Additionally patients with MPS will be eligible. Those patients with MDS or MPS with > 5% marrow blasts (including those with transformation to AML) must receive cytotoxic chemotherapy and achieve < 5% marrow blasts at time of transplant.

Are the trial subjects under 18? no
Number of subjects for this

Exclusion Criteria

1. Patients with rapidly progressive intermediate or high grade NHL.
2. CNS involvement with disease refractory to intrathecal chemotherapy. For LP requirement, see Appendix N.
3. Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
4. Females who are pregnant.
5. Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years.
6. Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month.
7. Organ dysfunction.
a. Cardiac ejection fraction < 35%. Ejection fraction is required if there is a history of anthracycline exposure or history of cardiac disease.
b. Pulmonary:
i) DLCO < 40% and/or receiving supplementary continuous oxygen.
ii) The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules.
c. Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. Patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3 mg/dL, and symptomatic biliary disease.
d. Karnofsky scores < 60 (see appendix B).
8. HIV positive patients.
9. Active bacterial or fungal infections unresponsive to medical therapy.
10. All patients receiving voriconazole therapy and who are then randomized to ARM 3 must have voriconazole discontinued (because of the risk of sudden death with concurrent rapamycin therapy) and if indicated, an alternative antifungal therapy should be initiated.
11. The addition of cytotoxic agents for cytoreduction” with the exception of Gleevec (imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified