URMC Related Haplo-identical Donor BMT (HaploOnly)

University of Rochester

Status and phase: Completed; Phase 1

Conditions: Myelofibrosis; Multiple Myeloma; Immune Deficiencies; Lymphoma; Hematological Disease; Solid Tumors

Treatments: Drug: Fludarabine; Drug: Post-Stem Cell Infusion Mesna; Drug: Melphalan; Drug: Busulfan; Drug: Pre-Stem Cell Infusion Mesna; Drug: Post-Stem Cell Infusion Cyclophosphamide; Procedure: Stem Cell Infusion; Drug: Thiotepa; Drug: Pre-Stem Cell Infusion Cyclophosphamide; Radiation: Total Body Irradiation 1200 cGy

Study type: Interventional

Funder types: Other

Identifiers

NCT02660281

UBMT 15056

Details and patient eligibility

About

This study will be a single-center treatment protocol, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit.

Full description

This study will be a single-center treatment protocol with five possible preparative regimens, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit. Enrolled patients will receive chemotherapy +/- radiation as a pre-transplant conditioning regimen. Patients will then receive haploidentical stem cells, either bone marrow or mobilized peripheral blood, followed by GvHD prophylaxis that will include cyclophosphamide. Multiple data points will be collected prior to, during, and following transplantation to ensure safety of the process and to evaluate the stated objectives.

Enrollment: 74 patients

Sex: All

Ages: 6 months to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patient Age:

• Pediatric (ages 6 months to 18 years)
• Adult (ages 18-75 years)

Disease:

Congenital and Other Non-malignant Disorders

• Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome)
• Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta)
• Metabolic disorders (e.g. Hurler's Syndrome)
• Hemoglobinopathies (e.g. Sickle Cell Disease, Thalassemia)
• Severe aplastic anemia

High-Risk Leukemias

Acute Myelogenous Leukemia

• Refractory to standard induction therapy (more than 1 cycle required to achieve remission)
• Recurrent (in CR≥2)
• Treatment-related AML or MDS
• Evolved from myelodysplastic syndrome
• Presence of Flt3 abnormalities
• FAB M6 or M7
• Adverse cytogenetics

Myelodysplastic Syndrome

Acute Lymphoblastic Leukemia including T lymphoblastic leukemia

• Refractory to standard induction therapy (time to CR >4 weeks)
• Recurrent (in CR ≥2)
• WBC count >30,000/mcL at diagnosis
• Age >30 at diagnosis
• Adverse cytogenetics, such as (t(9:22), t(1:19), t(4:11), other MLL rearrangements.

Chronic Myelogenous Leukemia in accelerated phase or blast crisis

Biphenotypic or undifferentiated leukemia

Burkitt's leukemia or lymphoma

Lymphoma:

• Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemosensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous SCT
• Marginal zone or follicular lymphoma that is progressive after at least two prior therapies

Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible for an autologous HSCT

Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and disease status

Graft failure following prior related donor, unrelated donor or UCB transplant

Myelofibrosis

Exclusion criteria

1. Patient Age below 6 months or over 75 years
2. Availability of a 10/10 HLA-matched related or unrelated donor within a reasonable time-frame dictated by the clinical urgency of the transplant
3. Autologous HSCT < 6 months prior to proposed haplo-SCT
4. Pregnant or breast-feeding
5. Current uncontrolled infection
6. Evidence of HIV infection or positive HIV serology
7. Anti-donor HLA antibodies with positive crossmatch and unsuccessful -

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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74 participants in 5 patient groups

Full Intensity TBI-based Conditioning

Other group

Description:

Total Body Irradiation 1200 cGy of 150 cGy over 4 or 5 days, days -5 or -4 to -1 Fludarabine 30 mg/m2/day x 3 days, days -6, -5, -4 Stem Cell Infusion, day 0 Post- Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Mesna 50 mg/kg/day x 2 days, days +3 and +4

Treatment:

Radiation: Total Body Irradiation 1200 cGy

Procedure: Stem Cell Infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide

Drug: Post-Stem Cell Infusion Mesna

Drug: Fludarabine

Full Intensity Chemo-Only Conditioning

Other group

Description:

Fludarabine 25 mg/m2/day x 5 days, days -6, -5, -4, -3, -2 Busulfan 130 mg/m2/day x 4 days, days -6, -5, -4, -3 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell Infusion Mesna 14.5 mg/kg/day x 2 days, days -3 and -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, days +3 and +4

Treatment:

Drug: Pre-Stem Cell Infusion Cyclophosphamide

Procedure: Stem Cell Infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide

Drug: Pre-Stem Cell Infusion Mesna

Drug: Busulfan

Drug: Post-Stem Cell Infusion Mesna

Drug: Fludarabine

Reduced Intensity Conditioning

Other group

Description:

Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4

Treatment:

Procedure: Stem Cell Infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide

Drug: Melphalan

Drug: Post-Stem Cell Infusion Mesna

Drug: Fludarabine

Non-Myeloablative Conditioning

Other group

Description:

Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell InfusionMesna 14.5 mg/kg/day x 2 days, days -3 and -2 Total Body Irradiation 200 cGy, day -1 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, day +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, day +3 and +4

Treatment:

Drug: Pre-Stem Cell Infusion Cyclophosphamide

Radiation: Total Body Irradiation 1200 cGy

Procedure: Stem Cell Infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide

Drug: Pre-Stem Cell Infusion Mesna

Drug: Post-Stem Cell Infusion Mesna

Drug: Fludarabine

Reduced Intensity Conditioning with Addition of Thiotepa

Other group

Description:

Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Thiotepa 8 mg/kg, day -3 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4

Treatment:

Drug: Thiotepa

Procedure: Stem Cell Infusion

Drug: Post-Stem Cell Infusion Cyclophosphamide

Drug: Melphalan

Drug: Post-Stem Cell Infusion Mesna

Drug: Fludarabine