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

  • STATUS
    Recruiting
  • End date
    Dec 31, 2022
  • participants needed
    20
  • sponsor
    Srinivas Devarakonda
Updated on 29 March 2021
cancer
fludarabine
tacrolimus
mycophenolate mofetil
cyclophosphamide
carbon monoxide
ejection fraction
monoclonal antibodies
melphalan
cell transplantation
tumor cells
monoclonal protein
daratumumab
diffusion capacity of the lung for carbon monoxide

Summary

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.

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.

Details
Condition Recurrent Plasma Cell Myeloma
Treatment cyclophosphamide, mycophenolate mofetil, melphalan, allogeneic hematopoietic stem cell transplantation, Fludarabine, Tacrolimus, Daratumumab
Clinical Study IdentifierNCT04205240
SponsorSrinivas Devarakonda
Last Modified on29 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 75 yrs?
Gender: Male or Female
Do you have Recurrent Plasma Cell Myeloma?
Do you have any of these conditions: Do you have Recurrent Plasma Cell Myeloma??
Do you have any of these conditions: Do you have Recurrent Plasma Cell Myeloma??
Do you have any of these conditions: Do you have Recurrent Plasma Cell Myeloma??
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
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