Calcineurin Inhibitor-Free GVHD Prevention Regimen After Related Haplo PBSCT

H. Lee Moffitt Cancer Center and Research Institute

Status and phase

Completed

Phase 1

Conditions

Hodgkin Lymphoma

Acute Leukemia in Remission

Multiple Myeloma

Non-Hodgkin's Lymphoma

Primary Myelofibrosis

Chronic Myeloid Leukemia

Myelodysplastic Syndromes

Chronic Myelomonocytic Leukemia

Treatments

Drug: Granulocyte-colony stimulating factor (G-CSF)

Drug: Mycophenolate mofetil (MMF)

Radiation: Total body irradiation (TBI)

Procedure: Peripheral Blood Hematopoietic Cell Transplantation (HCT)

Drug: Busulfan

Drug: Cyclophosphamide

Drug: Sirolimus (SIR)

Drug: Fludarabine

Study type

Interventional

Funder types

Other

Identifiers

NCT03018223

MCC-18766

Details and patient eligibility

About

The purpose of this study is to find out if a combination of drugs (these are called: cyclophosphamide, sirolimus, and mycophenolate mofetil) will protect participants better against graft vs. host disease (GVHD) after receiving a hematopoietic cell transplant from a related partially matched (haploidentical) donor. As part of the treatment for their blood cancer, participants need a hematopoietic cell transplantation (HCT) to improve their chances of cure. In any HCT, after the stem cell infusion is given, a combination of drugs is needed to prevent GVHD and facilitate acceptance of the graft.

Enrollment

32 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Patient Participants:

Age: Must be older than 18 years, no upper age limit.
Karnofsky performance status: Full intensity conditioning, 80-100%; reduced intensity conditioning, 60-100%.
Vital organ function: a) Cardiac: Left ventricular ejection fraction must be > 45% assessed by multigated acquisition (MUGA) scan or echocardiogram. No myocardial infarction within 6 months of transplant evaluation. b) Pulmonary: forced expiratory volume at one second (FEV1), forced vital capacity (FVC), and adjusted diffusing capacity of the lungs for carbon monoxide (DLCO) must be ≥ 50% of predicted values. c) Liver: Transaminases (AST, ALT) less than 2 times upper limit of normal values. d) Kidney: Estimated creatinine clearance ≥ 50 cc/min.
Signed informed consent.
Included disease conditions and remission status: a) Acute leukemia in First Complete Remission (CR1) or second/subsequent CR. b) Chronic myeloid leukemia, primary myelofibrosis, chronic myelomonocytic leukemia. c) Int-2 or high risk myelodysplastic syndrome (MDS). d) Hodgkin lymphoma beyond CR1 with chemosensitive disease, Stable Disease (SD) may be included if no mass >3 cm. e) Non-Hodgkin lymphoma in high risk CR1 or subsequent CR (by clinical, cytogenetic or molecular criteria), primary induction failure (PIF) or relapsed with chemosensitive disease. SD may be included if no mass >3 cm. f) Multiple myeloma in CR/Very Good Partial Response (VGPR).

Donor Participants:

Per Moffitt Cancer Center (MCC) Blood and Marrow Transplant (BMT) program practices, an allele level matched (8/8 HLA A, B, C and DR) sibling or unrelated donor is preferred. If a matched donor is not found, mismatched unrelated or haploidentical donors may be considered.
If a haploidentical donor is considered, parents, children, full siblings and in selected cases, extended family, will have high resolution typing at the MCC HLA laboratory. A familiar haploidentical donor is chosen among those who share at least one HLA-A, B, C, DRB1 and DQB1 haplotype with the patient.
Patient will be screened for antibodies targeting mismatched HLA antigens in potential haploidentical donors (donor specific antibodies, DSA). Antibody screen and confirmatory testing using Luminex single antigen-bead test will be done.
Among several potential donors, will choose in order of priority: a) Matched cytomegalovirus (CMV) immunoglobulin G (IgG) serologic status between donor and recipient. b) ABO blood group system-matched donor preferred, then minor ABO mismatch, then major ABO mismatch. c) Younger donor preferred: child, then sibling, and then parent. d) For male recipient, male donor will be preferred. Avoid mother as a donor unless no other choices.

Exclusion criteria

Patient Participants:

Uncontrolled active bacterial, viral, fungal infection.
Prior allogeneic HCT.
Unwilling to comply with study requirements.
Active, progressive or advanced disease based on diagnosis.

Trial design

Primary purpose

Prevention

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

32 participants in 1 patient group

Conditioning/HCT/GVHD Prophylaxis

Experimental group

Description:

Pre-HCT Conditioning, HCT, GVHD Prophylaxis. 1. Conditioning regimen: To reduce heterogeneity, two commonly used myeloablative (MAC) and reduced intensity (RIC) regimens are permitted on this trial. Myeloablative conditioning: fludarabine, busulfan. Reduced intensity conditioning: fludarabine, cyclophosphamide, total body irradiation. 2. Peripheral blood hematopoietic cell transplantation 3. Graft vs. Host Disease (GVHD) prevention treatment: cyclophosphamide, mycophenolate mofetil, sirolimus. 4. Growth factor support: G-CSF

Treatment: