TMI With HD Mel in ASCT for R/R Multiple Myeloma (BMT-03)

University of Illinois

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma, Refractory to Standard Treatment; Multiple Myeloma, Relapsed

Treatments: Radiation: Total Marrow Irradiation; Drug: Filgrastim (G-CSF); Procedure: Autologous transplant; Drug: Melphalan

Study type: Interventional

Funder types: Other

Identifiers

NCT02043847

2013-0201 (Other Identifier)

Details and patient eligibility

About

In this phase I trial, patients with relapsed or refractory multiple myeloma will receive standard autologous stem cell transplant conditioned with high dose melphalan. In addition to Melphalan, the conditioning will include targeted total marrow irradiation (TMI). This is a conventional 3+3 phase I trial with increasing doses of TMI from minimum 3Gy to Maximum 9Gy.

Full description

In this phase I trial, patients with relapsed or refractory multiple myeloma will receive standard high dose melphalan with autologous stem cell rescue. In addition the pre-transplant conditioning will include targeted total marrow irradiation (TMI). This conventional 3+3 phase I trial will increase the dose of TMI until the maximum tolerated dose (MTD) is reached. Initial patients enrolled will receive the lowest possible dose of 3Gy. Maximum dose will be 9Gy.

Enrollment: 12 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients meeting criteria for symptomatic myeloma
2. Patients who have progressive myeloma following initial induction (patients may have received any number of treatment regimens including prior autologous transplant)
3. Patient age 18-75 years at time of enrollment
4. Karnofsky performance status of ≥70
5. Cardiac function: LVEF >40%
6. Hepatic: Bilirubin <2x upper limit of normal and ALT and AST < 2.5x the upper limit of normal
7. Renal: Creatinine clearance of >30mL/min, estimated or calculated
8. Pulmonary: DLCO, FEV1, FVC >50% of predicted (after correction for hemoglobin)

Exclusion criteria

1. Patients with diagnosis of plasma cell leukemia
2. Patients with truly non secretory myeloma (patients with light chain disease are eligible)
3. Pregnant or breast-feeding
4. Uncontrolled viral, fungal or bacterial infection Note: Infection is permitted if there is evidence of response to medication. Eligibility of HIV infected patients will be determined on a case-by-case basis.
5. Patients who have undergone prior allogeneic stem cell transplant
6. Prior solid organ transplant
7. Patients receiving prior radiation to more than 20% of bone marrow containing areas

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 3 patient groups

Cohort 1Total Marrow Irradiation (TMI) 3Gy

Experimental group

Description:

3Gy with standard high dose melphalan prior to autologous stem cell rescue

Treatment:

Radiation: Total Marrow Irradiation

Procedure: Autologous transplant

Radiation: Total Marrow Irradiation

Drug: Filgrastim (G-CSF)

Drug: Melphalan

Procedure: Autologous transplant

Drug: Filgrastim (G-CSF)

Drug: Melphalan

Procedure: Autologous transplant

Radiation: Total Marrow Irradiation

Drug: Filgrastim (G-CSF)

Drug: Melphalan

Cohort 2 Total Marrow Irradiation (TMI) 6Gy

Experimental group

Description:

6Gy with standard high dose melphalan prior to autologous stem cell rescue

Treatment:

Radiation: Total Marrow Irradiation

Procedure: Autologous transplant

Radiation: Total Marrow Irradiation

Drug: Filgrastim (G-CSF)

Drug: Melphalan

Procedure: Autologous transplant

Drug: Filgrastim (G-CSF)

Drug: Melphalan

Procedure: Autologous transplant

Radiation: Total Marrow Irradiation

Drug: Filgrastim (G-CSF)

Drug: Melphalan

Cohort 3 Total Marrow Irradiation (TMI) 9Gy

Experimental group

Description:

9Gy with standard high dose melphalan prior to autologous stem cell rescue

Treatment:

Radiation: Total Marrow Irradiation

Procedure: Autologous transplant

Radiation: Total Marrow Irradiation

Drug: Filgrastim (G-CSF)

Drug: Melphalan

Procedure: Autologous transplant

Drug: Filgrastim (G-CSF)

Drug: Melphalan

Procedure: Autologous transplant

Radiation: Total Marrow Irradiation

Drug: Filgrastim (G-CSF)

Drug: Melphalan