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Pre-BMT :

* Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
* Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
* Day -1: 400 cGy total body irradiation (TBI) administered in a single fraction

Day 0: Allogeneic blood or marrow transplantation (BMT)

Post-Transplantation Immunosuppression Consisting of:

* Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
* Day 5: Sirolimus loading dose 6 mg PO once
* Day 5 thru Day 35: Mycophenolate Mofetil (MMF) 15 mg/kg PO TID (maximum daily dose 3 g/day)
* Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL

Pre-BMT:

* Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
* Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
* Day -1: 400 cGy TBI administered in a single fraction

Day 0: BMT

Post-Transplantation Immunosuppression Consisting of:

* Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
* Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
* Day 5 thru Day 180: Tacrolimus 1 mg administered IV QD

Pre-PBSCT:

* Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
* Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
* Day -1: 400 cGy TBI administered in a single fraction

Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)

Post-Transplantation Immunosuppression Consisting of:

* Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
* Day 5: Sirolimus loading dose 6 mg PO once
* Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
* Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL

Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day

Cytoxan

400 cGy TBI administered in a single fraction

Total Body Irradiation

Allogeneic Blood or Marrow Transplant

Peripheral Blood Stem Cell Transplant

Mycophenolate Mofetil

Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily

Richard Ambinder, MD

Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce

If transplantation using mismatched unrelated donors or non-first-degree relatives could be performed with an acceptable toxicity profile, an important unmet need would be served. Towards this goal, the current study extends our platform of nonmyeloablative, partially HLA-mismatched bone marrow transplant (BMT) and Peripheral Blood Stem Cell Transplant (PBSCT) to the use of such donors, investigating up to several postgrafting immunosuppression regimens that incorporate high-dose Cy. Of central interest is the incorporation of sirolimus into this postgrafting immunosuppression regimen.

The primary goal for phase 1 is to identify a transplant regimen associated with acceptable rates of severe acute GVHD and NRM by Day 100 and for phase 2 estimate the 6-month probability of survival without having had acute grade III- IV GVHD or graft failure.

Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies

Reduced Intensity, Partially HLA Mismatched Allogeneic BMT for Hematologic Malignancies Using Donors Other Than First-degree Relatives

Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable rates of severe acute GVHD (\< 25%).

Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable rates transplant-related NRM (\< 20%).

Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors.

All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.

All suspected cases of acute GVHD must be confirmed histologically by biopsy of an affected organ (skin, liver, or gastrointestinal tract). Date of symptom onset, date of biopsy confirmation of GVHD, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher GVHD and grade III-IV GVHD will be recorded.

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies	NCT01203722	Hematologic Mal...	Fludarabine Cytoxan Total Body Irra... Allogeneic Bloo... Peripheral Bloo... Mycophenolate M... Sirolimus Tacrolimus	6 Months - 75 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies	NCT01203722	Hematologic Mal...	Fludarabine Cytoxan Total Body Irra... Allogeneic Bloo... Peripheral Bloo... Mycophenolate M... Sirolimus Tacrolimus	6 Months - 75 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies	NCT01203722	Hematologic Mal...	Fludarabine Cytoxan Total Body Irra... Allogeneic Bloo... Peripheral Bloo... Mycophenolate M... Sirolimus Tacrolimus	6 Months - 75 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for allogeneic blood or marrow transplant