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

NCT ID: NCT02556931

Last Updated: 2022-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2021-04-30

Brief Summary

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.

Detailed Description

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.

Conditions

Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Myeloproliferative Disorders; Multiple Myeloma; Plasma Cell Neoplasm; Plasma Cell Dyscrasia; Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia; Plasma Cell Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PBSCT D90

Non-myeloablative peripheral blood stem cell transplant (PBSCT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Tacrolimus will be stopped at either Day 90 or Day 180 depending on GVHD status.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Total body irradiation

Intervention Type: RADIATION

Day -1: 200 cGy in a single fraction

Tacrolimus

Intervention Type: DRUG

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 mofetil

Intervention Type: DRUG

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

PBSCT D60

Non-myeloablative peripheral blood stem cell transplant (PBSCT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Tacrolimus will be stopped at either Day 60 or Day 180 depending on GVHD status.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Total body irradiation

Intervention Type: RADIATION

Day -1: 200 cGy in a single fraction

Tacrolimus

Intervention Type: DRUG

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 mofetil

Intervention Type: DRUG

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

Interventions

Fludarabine

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Total body irradiation

Day -1: 200 cGy in a single fraction

Intervention Type: RADIATION

Tacrolimus

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.

Intervention Type: DRUG

Mycophenolate mofetil

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

Intervention Type: DRUG

Other Intervention Names

Fludara; Cytoxan; Cy; CTX; TBI; Prograf; FK506; FK-506; MMF; CellCept

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amy E DeZern, MD

Role: PRINCIPAL_INVESTIGATOR

410-502-7208

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00080399

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA015396

Identifier Type: NIH

Identifier Source: secondary_id

View Link

J15165

Identifier Type: -

Identifier Source: org_study_id