Reduce Intensity Conditioning Donor Stem Cell Transplant for the Treatment of Relapsed Multiple Myeloma

Srinivas Devarakonda

Status and phase

Terminated

Phase 2

Conditions

Recurrent Plasma Cell Myeloma

Treatments

Drug: Mycophenolate Mofetil

Drug: Cyclophosphamide

Drug: Tacrolimus

Drug: Melphalan

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Drug: Fludarabine

Biological: Daratumumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04205240

NCI-2019-07892 (Registry Identifier)

OSU-19190

Details and patient eligibility

About

This phase II trial studies how well a reduced intensity conditioning regimen after donor stem cell transplant works in treating patients with multiple myeloma that has come back (relapsed). Drugs used in chemotherapy, such as cyclophosphamide, tacrolimus, and mycophenolate mofetil, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving a reduce intensity conditioning regimen consisting of cyclophosphamide, tacrolimus, mycophenolate mofetil, and daratumumab after donor stem cell transplant may improve survival and reduce the risk of multiple myeloma coming back.

Full description

PRIMARY OBJECTIVE:

I. To determine the 2-year progression-free survival (PFS) for haploidentical, matched or mismatched, related or unrelated reduce intensity allogenic hematopoietic stem cell transplantation (allo HSCT) in relapsed multiple myeloma (MM) patients.

SECONDARY OBJECTIVES:

I. To determine 2 year overall survival (OS). II. To determine the cumulative incidence of grade II-IV acute-graft-versushost-disease (aGVHD) at day 100 and 180.

III. To determine the 100 days, 1 year and 2 year cumulative incidence of treatment-related mortality (TRM).

IV. To assess one-year GVHD-free relapse-free survival (GRFS). V. To determine the cumulative incidence of chronic graft-versus-hostdisease (cGVHD) Va. To assess overall and best response rates 100 days after allo HCT, 3 months, 6 months and every 6 months thereafter until end of daratumumab maintenance.

VI. To determine rate of relapse after allo HSCT followed by maintenance. VII. To determine rate of minimal residual disease (MRD) negativity using next generation sequencing (Food and Drug Administration [FDA] approved) in patients achieving a very good partial response (VGPR) or better.

CORRELATIVE OBJECTIVE:

I. To determine immune reconstitution pattern on days +30, +100, +180 and +365 following allo HSCT.

OUTLINE:

Patients receive fludarabine intravenously (IV) on days -5 to -2 and melphalan IV on days -3 to -2, then undergo stem cell transplantation on day 0. Patients receive cyclophosphamide on days 3 and 4, tacrolimus orally (PO) or twice daily (BID) or IV starting on day 5, and mycophenolate mofetil IV or PO three times daily (TID) on days 5 to 35. Patients also receive daratumumab IV starting between day 90-150 for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 2 years post stem cell transplantation.

Enrollment

1 patient

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with a partial response (PR) or better prior to allo-transplantation
Relapsed MM with chemo sensitivity disease, with or without prior autologous HSCT
First allogenic transplant
Donors can be haploidentical, mismatch or matched related or unrelated. Stem cell source will be peripheral blood except for haploidentical where stem cell source will be bone marrow
Ejection fraction >= 45%
Estimated creatinine clearance greater than 40 mL/minute
Diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% (adjusted for hemoglobin)
Forced expiratory volume in 1 second (FEV1) >= 50%
Total bilirubin < 2 x the upper limit of normal
Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x the upper normal limit
Signed informed consent

Exclusion criteria

Patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS), Waldenstrom macroglobulinemia
Uncontrolled bacterial, viral or fungal infection
Patients with prior malignancies < 3 years except resected basal cell/squamous cell carcinoma, treated carcinoma in-situ. Other cancers treated with curative intent < 3 years previously will not be allowed unless approved by the principal investigator
Female patients who are pregnant or breastfeeding. A negative pregnancy test will be required for all women of child bearing potential

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

1 participants in 1 patient group

Treatment (conditioning regimen, stem cell transplant)

Experimental group

Description:

Patients receive fludarabine IV on days -5 to -2 and melphalan IV on days -3 to -2, then undergo stem cell transplantation on day 0. Patients receive cyclophosphamide on days 3 and 4, tacrolimus PO BID or IV starting on day 5, and mycophenolate mofetil IV or PO TID on days 5 to 35. Patients also receive daratumumab IV starting between days 90-150 for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

Treatment: