Shorter Course Tacro After NMA, Related Donor PBSCT With High-dose Posttransplant Cy for Hard-to-Engraft Malignancies

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins117 enrolled

Overview

To see if it is possible to use short-duration tacrolimus after a peripheral blood stem cell transplant in certain malignancies that are considered difficult to engraft.

The main goal is to learn whether a drug called tacrolimus, which is an immune-lowering drug (an immunosuppressant) given after transplant to help prevent certain complications, can be given safely for a shorter period of time than it has been in the past. The experiences with immunosuppression duration with other allogeneic HSCT platforms cannot be directly extrapolated to the high-dose posttransplantation cyclophosphamide platform (another type of immunosuppressant given after transplant to help prevent GVHD). There are presently no published data on the minimum required duration of tacrolimus after nonmyeloablative HSCT that includes high-dose Cy as part of postgrafting immunosuppression. The effectiveness of high-dose posttransplantation Cy in GVHD prevention, however, permits the investigation of this question. At the present time there are few or no cures for diseases studied on this trial outside of a bone marrow or peripheral blood transplant. The peripheral blood for this transplant comes from a relative who is a half-match or "haplo" match to the participant. Possible donors include parents, siblings, and children. In order to help the bone marrow grow, or "take", inside the body, participants will receive chemotherapy and radiation before the transplant. After the transplant participants will receive high doses of cyclophosphamide (Cytoxan®) along with other medications to lower the immune system, such as tacrolimus. These medications may lower the risk of graft versus host disease (GVHD) and of rejection of the peripheral blood graft.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

117

Interventions

FludarabineDRUG

Days -6 through -2: 30 mg/m\^2 IV daily

CyclophosphamideDRUG

Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily

Total body irradiationRADIATION

Day -1: 200 cGy in a single fraction

TacrolimusDRUG

Start on Day 5 through either Day 60 or Day 90 depending on cohort assignment. May be continued through Day 180 depending on GVHD status.

Mycophenolate mofetilDRUG

Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * Presence of a suitable related HLA-haploidentical or -matched stem cell donor, or a 10/10 matched unrelated donor * Eligible diagnoses: myelodysplastic syndrome (MDS) with at least 1 poor-risk feature; small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with 17p deletion or with progression \< 6 months after a second or greater treatment regimen; T-cell prolymphocytic leukemia (PLL) in partial response or better; interferon- or tyrosine-kinase-refractory chronic myeloid leukemia (CML), or CML in second or subsequent chronic phase; Philadelphia chromosome negative (Ph-) myeloproliferative disease, including myelofibrosis; Multiple myeloma or plasma cell leukemia in partial response or better; Hematologic malignancy in complete remission with minimal residual disease (MRD) detectable by conventional cytogenetics, FISH, flow cytometry, or molecular testing * Any previous autologous transplant must have occurred \> 3 months ago * Left ventricular ejection fraction (LVEF) \>= 35%, or shortening fraction \> 25% * Bilirubin \<= 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis) * AST and ALT \<= 5 x institutional upper limit of normal * FEV1 and FVC \>= 40% of predicted; if unable to perform pulmonary function testing, oxygen saturation \> 92% on room air * ECOG performance status \<= 2, or Karnofsky/Lansky status \>= 60 Exclusion Criteria: * Pregnancy or active breastfeeding * Uncontrolled active infection * Previous allogeneic transplant * Active extramedullary leukemia or active central nervous system (CNS) malignant disease

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D90 Cohort)

This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 90.

Time frame: Day 90

Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D60 Cohort)

This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 60.

Time frame: Day 60

Secondary Outcomes

Number of Participants With Grades III-IV Acute GVHD, Days 90-180 (D90)

Number of participants who experience grade III or IV acute GVHD between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.

Time frame: Between Day 90 and Day 180

Number of Participants With Grades III-IV Acute GVHD, Days 60-180 (D60)

Number of participants who experience grade III or IV acute GVHD between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.