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

NCT04205240 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: OSU-19190NCI-2019-07892
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• 2-year Progression-free Survival (PFS)

  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.

  From the date of transplant until the date of relapse or date of death from any cause, assessed at 2 years

Secondary Outcomes (10)

• Incidence of Adverse Events

  Up to 2 years post-transplant

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

  Up to 6 weeks

• Rate of Relapse

  From the date of transplant to relapse treating death from any cause as a competing risk, assessed up to 2 years

• Overall Survival (OS)

  From the date of transplant to death or last contact date if no death, assessed up to 2 years

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

  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

Other Outcomes (1)

• Rate of Minimal Residual Disease-negativity

  Baseline up to 365 days post-transplant

Study Arms (1)

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Biological: Daratumumab; Drug: Fludarabine; Drug: Melphalan; Drug: Mycophenolate Mofetil; Drug: Tacrolimus

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic hematopoietic stem cell transplantation

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (conditioning regimen, stem cell transplant)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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 BIOLOGICAL

Given IV

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Treatment (conditioning regimen, stem cell transplant)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (conditioning regimen, stem cell transplant)

Melphalan DRUG

Given IV

Also known as: 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 DRUG

Given IV or PO

Also known as: Cellcept, MMF

Treatment (conditioning regimen, stem cell transplant)

Tacrolimus DRUG

Given PO or IV

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (conditioning regimen, stem cell transplant)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Srinivas Devarakonda: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Stem Cell Transplantation; Cyclophosphamide; daratumumab; fludarabine; Melphalan; Mycophenolic Acid; Tacrolimus

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Limitations and Caveats

The trial was terminated early due to poor patient accrual

Results Point of Contact

• Title: Dr. Srinivas Devarakonda
• Organization: The Ohio State University Comprehensive Cancer Center

Srinivas.Devarakonda@osumc.edu

614-293-3196

Study Officials

• Srinivas Devarakonda, M.D.

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 19, 2019
• Study Start: December 22, 2020
• Primary Completion: May 8, 2021
• Study Completion: November 22, 2021
• Last Updated: September 28, 2023
• Results First Posted: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)