Clinical Trial: NCT04205240 - My Cancer Genome

NCT04205240

Description:

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.

Related Conditions:

Multiple Myeloma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04205240

Trial Eligibility

Document

Title

Brief Title: 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

Clinical Trial IDs

ORG STUDY ID: OSU-19190
SECONDARY ID: NCI-2019-07892
NCT ID: NCT04205240

Conditions

Recurrent Plasma Cell Myeloma

Interventions

Drug	Synonyms	Arms
Cyclophosphamide	(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719	Treatment (conditioning regimen, stem cell transplant)
Daratumumab	Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414	Treatment (conditioning regimen, stem cell transplant)
Fludarabine	Fluradosa	Treatment (conditioning regimen, stem cell transplant)
Melphalan	Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813	Treatment (conditioning regimen, stem cell transplant)
Mycophenolate Mofetil	Cellcept, MMF	Treatment (conditioning regimen, stem cell transplant)
Tacrolimus	FK 506, Fujimycin, Hecoria, Prograf, Protopic	Treatment (conditioning regimen, stem cell transplant)

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
Treatment (conditioning regimen, stem cell transplant)	Experimental	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.	Cyclophosphamide Daratumumab Fludarabine Melphalan Mycophenolate Mofetil Tacrolimus

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

Maximum Eligible Age:	75 Years
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	2-year progression-free survival (PFS)
Time Frame:	From the date of transplant until the date of relapse or date of death from any cause, assessed at 2 years
Safety Issue:
Description:	Patients who do not relapse or die will be censored at the date of last clinical assessment. Kaplan-Meier curves will be generated to estimate the PFS rates at 2 years posttransplant. To evaluate the potential association between patient characteristics and PFS, the log-rank test will be used to compare the PFS curves and Cox proportional hazard regression model will be used to estimate the hazard ratio.

Secondary Outcome Measures

Measure:	Incidence of adverse events
Time Frame:	Up to 2 years post-transplant
Safety Issue:
Description:	Adverse events by grade will be summarized. The occurrence of grade 3+ adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) will be summarized as well. Adverse events will initially be reviewed regardless of attribution, but also according to whether adverse events are possibly, probably, or definitely related to treatment.

Measure:	Cumulative incidence of grade II-IV acute graft-versus host disease (GvHD (aGVHD)
Time Frame:	Up to 6 weeks
Safety Issue:
Description:	The event will be onset of grade II-IV aGvHD and time to aGvHD will be defined as the period of time from transplantation to the event of aGvHD. Death and early relapse without aGvHD will be competing risks. Cumulative incidence rate of aGVHD with 95% confidence intervals will be estimated from the cumulative incidence curves. To evaluate the association between patient characteristics and aGVHD, the Gray's test accounting for competing risks will be used to compare the cumulative incidence curves and a proportional hazards model for the sub distribution of competing risks will be used to estimate the hazard ratio. The cumulative incidence of chronic GVHD (cGVHD) will be similarly analyzed.

Measure:	Rate of relapse
Time Frame:	From the date of transplant to relapse treating death from any cause as a competing risk, assessed up to 2 years
Safety Issue:
Description:	Patients without relapse or death will be censored at last clinical assessment date. The similar analysis approach used for outcome of aGVHD will be applied.

Measure:	Overall survival (OS)
Time Frame:	From the date of transplant to death or last contact date if no death, assessed up to 2 years
Safety Issue:
Description:	A similar analysis approach described above for PFS will be applied for the OS analysis.

Measure:	1- year GVHD-free Relapse-free Survival (GRFS)
Time Frame:	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
Safety Issue:
Description:	Patients who do not experience an event will be censored at the date of last clinical assessment. A similar analysis approach described above for PFS will be applied for the GRFS analysis.

Measure:	100-day cumulative incidence of treatment-related mortality (TRM)
Time Frame:	From the date of transplant to date of death, assessed up to 100 days
Safety Issue:
Description:	The event will be death due to reasons other than disease. The competing risk for non relapsed mortality (NRM) will be death due to disease. The cumulative incidence curve accounting competing risks will be generated to estimate the cumulative incidence rate at various time points.

Measure:	1-year cumulative incidence TRM
Time Frame:	From the date of transplant to date of death, assessed at 1 year
Safety Issue:
Description:	The event will be death due to reasons other than disease. The competing risk for NRM will be death due to disease. The cumulative incidence curve accounting competing risks will be generated to estimate the cumulative incidence rate at various time points.

Measure:	2-year cumulative incidence of TRM
Time Frame:	From the date of transplant to date of death, assessed at 2 years
Safety Issue:
Description:	The event will be death due to reasons other than disease. The competing risk for NRM will be death due to disease. The cumulative incidence curve accounting competing risks will be generated to estimate the cumulative incidence rate at various time points.

Measure:	Overall response rate
Time Frame:	Up to 2 years post-transplant
Safety Issue:
Description:	The proportion of each type of response with a 95% confidence interval (CI) will be reported for all evaluable patients, assuming a binomial distribution.

Measure:	Best response rate
Time Frame:	Up to 2 years post-transplant
Safety Issue:
Description:	The proportion of each type of response with a 95% CI will be reported for all evaluable patients, assuming a binomial distribution.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Srinivas Devarakonda

Last Updated

March 22, 2021

Clinical Trials /

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