NCT04205240 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2023-09-28

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

2-year Progression-free Survival (PFS)

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outcome · POSTED

Incidence of Adverse Events

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outcome · POSTED

Number of Patients With Grade II-IV Acute Graft-versus Host Disease (GvHD (aGVHD)

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outcome · POSTED

Rate of Relapse

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

1- Year GVHD-free Relapse-free Survival (GRFS)

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outcome · POSTED

100-day Cumulative Incidence of Treatment-related Mortality (TRM)

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outcome · POSTED

1-year Cumulative Incidence TRM

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outcome · POSTED

2-year Cumulative Incidence of TRM

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outcome · POSTED

Overall Response Rate

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outcome · POSTED

Number of Patients With a Partial Response

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outcome · POSTED

Rate of Minimal Residual Disease-negativity

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
maximum Age: 75 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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.
intervention Names
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Cyclophosphamide
Biological: Daratumumab
Drug: Fludarabine
Drug: Melphalan
Drug: Mycophenolate Mofetil
Drug: Tacrolimus
label
Treatment (conditioning regimen, stem cell transplant)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (conditioning regimen, stem cell transplant)
description
Undergo allogeneic hematopoietic stem cell transplantation
name
Allogeneic Hematopoietic Stem Cell Transplantation
other Names
Allogeneic Hematopoietic Cell Transplantation
Allogeneic Stem Cell Transplantation
HSC
HSCT
Stem Cell Transplantation, Allogeneic
type
PROCEDURE
arm Group Labels
Treatment (conditioning regimen, stem cell transplant)
description
Given IV
name
Cyclophosphamide
other Names
(-)-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
type
DRUG
arm Group Labels
Treatment (conditioning regimen, stem cell transplant)
description
Given IV
name
Daratumumab
other Names
Anti-CD38 Monoclonal Antibody
Darzalex
HuMax-CD38
JNJ-54767414
type
BIOLOGICAL
arm Group Labels
Treatment (conditioning regimen, stem cell transplant)
description
Given IV
name
Fludarabine
other Names
Fluradosa
type
DRUG
arm Group Labels
Treatment (conditioning regimen, stem cell transplant)
description
Given IV
name
Melphalan
other Names
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
type
DRUG
arm Group Labels
Treatment (conditioning regimen, stem cell transplant)
description
Given IV or PO
name
Mycophenolate Mofetil
other Names
Cellcept
MMF
type
DRUG
arm Group Labels
Treatment (conditioning regimen, stem cell transplant)
description
Given PO or IV
name
Tacrolimus
other Names
FK 506
Fujimycin
Hecoria
Prograf
Protopic
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Will be defined as the proportion of patients who achieved minimal residual disease-negative status at the respective time point, in accordance with the International Myeloma Working Group criteria. Minimal residual disease was evaluated by next-generation sequencing using ClonoSEQ Assay.
measure
Rate of Minimal Residual Disease-negativity
time Frame
Baseline up to 365 days post-transplant

primary Outcomes

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.
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

secondary Outcomes

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
Incidence of Adverse Events
time Frame
Up to 2 years post-transplant
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
Number of Patients With Grade II-IV Acute Graft-versus Host Disease (GvHD (aGVHD)
time Frame
Up to 6 weeks
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
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
description
A similar analysis approach described above for PFS will be applied for the OS analysis.
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
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
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
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
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
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
1-year Cumulative Incidence TRM
time Frame
From the date of transplant to date of death, assessed at 1 year
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
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
Overall Response Rate
time Frame
Up to 2 years post-transplant
description
The proportion of each type of response with a 95% CI will be reported for all evaluable patients, assuming a binomial distribution.
measure
Number of Patients With a Partial Response
time Frame
Approximately 11 months

Full study description

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.

Source references