Clinical trial NCT04205240: Reduce Intensity Conditioning Donor Stem Cell Transplant for the Treatment of Relapsed Multiple Myeloma
Official title: Reduce Intensity Conditioning (RIC) Allogenic Hematopoietic Stem Cell Transplantation (Allo HSCT) for Patients With Relapsed Multiple Myeloma: A Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent Plasma Cell Myeloma
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2019-12-19
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 2-year Progression-free Survival (PFS)
timeFrame: From the date of transplant until the date of relapse or date of death from any cause, assessed at 2 years
Secondary outcomes:
measure: Incidence of Adverse Events
timeFrame: Up to 2 years post-transplant
measure: Number of Patients With Grade II-IV Acute Graft-versus Host Disease (GvHD (aGVHD)
timeFrame: Up to 6 weeks
measure: Rate of Relapse
timeFrame: From the date of transplant to relapse treating death from any cause as a competing risk, assessed up to 2 years
measure: Overall Survival (OS)
timeFrame: From the date of transplant to death or last contact date if no death, assessed up to 2 years
measure: 1- Year GVHD-free Relapse-free Survival (GRFS)
timeFrame: From the date of transplant until the date of grade II-IV acute GVHD, chronic GVHD, disease relapse or progression, or death from any cause, whichever occurs first, assessed at 1 year
measure: 100-day Cumulative Incidence of Treatment-related Mortality (TRM)
timeFrame: From the date of transplant to date of death, assessed up to 100 days
measure: 1-year Cumulative Incidence TRM
timeFrame: From the date of transplant to date of death, assessed at 1 year
measure: 2-year Cumulative Incidence of TRM
timeFrame: From the date of transplant to date of death, assessed at 2 years
measure: Overall Response Rate
timeFrame: Up to 2 years post-transplant
measure: Number of Patients With a Partial Response
timeFrame: Approximately 11 months
Other outcomes:
measure: Rate of Minimal Residual Disease-negativity
timeFrame: Baseline up to 365 days post-transplant
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Srinivas Devarakonda, M.D.
role: PRINCIPAL_INVESTIGATOR
References: