Tac, Mini-MTX, MMF Versus Tac, MTX for GVHD Prevention

NCT ID: NCT01951885

Last Updated: 2023-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-07
• Study Completion Date: 2021-08-11

Brief Summary

This randomized clinical trial studies standard GVHD prophylaxis with tacrolimus and methotrexate compared to tacrolimus, mycophenolate mofetil and a reduced-dose methotrexate in patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplant. Both mycophenolate mofetil and reduced-dose methotrexate, in combination with a calcineurin inhibitor, have been shown to be safe and effective in GVHD prevention with less toxicity than standard dose methotrexate. It is not yet known, however, whether this combination of mycophenolate mofetil and reduced-dose methotrexate with tacrolimus is more effective than tacrolimus and standard dose methotrexate in preventing GVHD.

Detailed Description

Study Design This is a prospective randomized trial to determine the effectiveness of different doses of GVHD prophylaxis on mucositis, engraftment and aGVHD. Study consists of two study groups of 50 subjects each.

Group A will receive Tac and MTX (15 mg/m2 day +1, 10 mg/m2 day +3, +6, +11). Group B will receive Tac, Mini-dose MTX (5 mg/m2 on day +1, +3, +6) and MMF.

Conditions

Chronic Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Biphenotypic Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Hodgkins Disease; Chronic Lymphocytic Leukemia; Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Group A (tacrolimus, methotrexate)

Participants receive tacrolimus IV over 24 hours beginning on day -1 (or tacrolimus orally beginning on day -3) and then PO BID after engraftment with a taper from day 100 to day 180 (in the absence of GVHD). Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Group Type: ACTIVE_COMPARATOR

tacrolimus

Intervention Type: DRUG

Tacrolimus 0.03 mg/kg/day beginning day -1 or tacrolimus 0.03mg/kg/dose BID orally beginning on day -3. If Tac is administered intravenously, it will be given over 24 hours and will be converted to oral administration 2 times a day when the patient has engrafted and/or can tolerate oral medication. Levels of Tac will be obtained to maintain a recommended target serum level of 5-12 ng/mL

methotrexate

Intervention Type: DRUG

MTX 15mg/m2 IV on day +1, followed by 10mg/m2 on day +3, +6, +11. If patient \< 10 kg then MTX will be given at 0.5 mg/kg IV on day +1. Then MTX will be given at 0.33 mg/kg on days +3, +6 and +11.

Group B (tacrolimus, methotrexate, mycophenolate mofetil)

Patients receive tacrolimus as in group A and methotrexate (low dose) IV on days 1, 3, and 6. Patients also receive oral mycophenolate mofetil BID beginning on day 1, with a taper from day 45 to day 100 (in the absence of GVHD).

Group Type: EXPERIMENTAL

tacrolimus

Intervention Type: DRUG

Tacrolimus 0.03 mg/kg/day beginning day -1 or tacrolimus 0.03mg/kg/dose BID orally beginning on day -3. If Tac is administered intravenously, it will be given over 24 hours and will be converted to oral administration 2 times a day when the patient has engrafted and/or can tolerate oral medication. Levels of Tac will be obtained to maintain a recommended target serum level of 5-12 ng/mL

Mycophenolate mofetil

Intervention Type: DRUG

Patients will receive Mycophenolate beginning on day +1. Patients \>40 kg will receive Mycophenolate 1000 mg twice a day. Mycophenolate should be given orally twice a day. IV formulation may be used if the patient cannot tolerate oral route. Patients \< 40 kg will receive MMF 45 mg/kg/day (15 mg/kg three times a day). MMF may be given orally or intravenously as per institutional protocol

Methotrexate (low dose)

Intervention Type: DRUG

MTX 5mg/m2 IV on day +1, +3, +6. If patient\<10 kg MTX will be given at 0.17 mg/kg on day +1, +3, and +6.

Interventions

tacrolimus

Tacrolimus 0.03 mg/kg/day beginning day -1 or tacrolimus 0.03mg/kg/dose BID orally beginning on day -3. If Tac is administered intravenously, it will be given over 24 hours and will be converted to oral administration 2 times a day when the patient has engrafted and/or can tolerate oral medication. Levels of Tac will be obtained to maintain a recommended target serum level of 5-12 ng/mL

Intervention Type: DRUG

methotrexate

MTX 15mg/m2 IV on day +1, followed by 10mg/m2 on day +3, +6, +11. If patient \< 10 kg then MTX will be given at 0.5 mg/kg IV on day +1. Then MTX will be given at 0.33 mg/kg on days +3, +6 and +11.

Intervention Type: DRUG

Mycophenolate mofetil

Patients will receive Mycophenolate beginning on day +1. Patients \>40 kg will receive Mycophenolate 1000 mg twice a day. Mycophenolate should be given orally twice a day. IV formulation may be used if the patient cannot tolerate oral route. Patients \< 40 kg will receive MMF 45 mg/kg/day (15 mg/kg three times a day). MMF may be given orally or intravenously as per institutional protocol

Intervention Type: DRUG

Methotrexate (low dose)

MTX 5mg/m2 IV on day +1, +3, +6. If patient\<10 kg MTX will be given at 0.17 mg/kg on day +1, +3, and +6.

Intervention Type: DRUG

Other Intervention Names

FK 506; Prograf; amethopterin; Folex; methylaminopterin; Mexate; MTX; Cellcept; MMF; amethopterin; Folex; methylaminopterin; Mexate; MTX

Eligibility Criteria

Inclusion Criteria

• Patients must have one of the following documented diseases:

• Chronic myelogenous leukemia
• Chronic lymphocytic leukemia
• Multiple myeloma
• Myelodysplasia
• Myeloproliferative disorder
• Non-Hodgkin's lymphoma
• Hodgkin's disease
• Acute myelogenous leukemia
• Acute lymphoblastic leukemia
• Acute biphenotypic leukemia
• Patients must be undergoing a myeloablative allogeneic hematopoietic cell transplant with one of the following conditioning regimens:

• Busulfan (≥ 12.8 mg/kg IV or PO) and cyclophosphamide (≥ 120 mg/kg)

--- Busulfan dose may be adjusted according to pharmacokinetics targeting a daily AUC of 5000 μmol-min/L, per institution standard of practice.

• Total body irradiation (TBI) (≥ 1200 cGy) and etoposide (60 mg/kg)
• TBI (≥ 1200 cGy) and cyclophosphamide (120 mg/kg)
• Patient must have achieved and be in complete morphologic remission prior to starting conditioning regimen
• Patient's donor must be a related or unrelated human leukocyte antigen (HLA) 8/8 allele-level match (HLA-A, B, C and DRB1)
• Adult patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; pediatric patients must have Lansky score ≥ 60%
• Patients must have a life expectancy of 100 days
• Patients must sign written informed consent

Exclusion Criteria

• Patients who have undergone any prior transplant
• Patients who are seropositive for human immunodeficiency virus (HIV)
• Patients with any medical illness or concurrent psychiatric illness which, in the investigators' opinion, cannot be adequately controlled with appropriate therapy
• Patients who are pregnant or lactating

• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Betty Hamilton, MD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Locations

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

References

Hamilton BK, Rybicki LA, Li H, Lucas T, Corrigan D, Kalaycio M, Sobecks R, Hanna R, Rotz SJ, Dean RM, Gerds AT, Jagadeesh D, Brunstein C, Sauter CS, Copelan EA, Majhail NS. Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention. Blood Adv. 2023 Aug 22;7(16):4505-4513. doi: 10.1182/bloodadvances.2023010310.

Reference Type: DERIVED

PMID: 37352262 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

CASE6Z13

Identifier Type: -

Identifier Source: org_study_id