Daratumumab After Stem Cell Transplant in Treating Patients With Multiple Myeloma

  • STATUS
    Recruiting
  • End date
    Dec 5, 2022
  • participants needed
    40
  • sponsor
    City of Hope Medical Center
Updated on 28 February 2022
platelet count
vasectomy
cancer
monoclonal antibodies
melphalan
cell transplantation
neutrophil count
chemotherapy regimen
monoclonal protein
daratumumab
high dose chemotherapy

Summary

This phase II trial studies how well daratumumab after a stem cell transplant works in treating patients with multiple myeloma. Monoclonal antibodies, such as daratumumab, may kill cancer cells that are left after chemotherapy.

Description

PRIMARY OBJECTIVE:

I. To determine the anti-myeloma activity of single-agent daratumumab post-autologous stem cell transplantation (ASCT) as assessed by progression-free survival at 1 year post ASCT.

SECONDARY OBJECTIVES:

I. To characterize the extent of minimal residual disease (MRD) pre-/post-consolidation treatment segment and at one year during the maintenance treatment segment.

II. To characterize and evaluate toxicities, including type, frequency severity, attribution, and duration (e.g., infections, secondary primary malignancies, peripheral neuropathy).

III. To obtain estimates of overall response rate (stringent complete response [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]), response duration, depth of response, clinical benefit response, and overall survival.

EXPLORATORY OBJECTIVES:

I. Quantify CD38+ cells from the peripheral blood mononuclear cells (PBMC) fraction, including T, natural killer (NK), and monocytic subsets using pre- and on-daratumumab treatment samples by flow cytometry.

II. Assess possible changes in CD38+ expression, as well as the co-receptor marker CD31, and possible correlation with response using pre- and on-daratumumab treatment samples by flow cytometry.

III. Assess cytokine levels in peripheral blood plasma. IV. Quantify CD38+ cells from the bone marrow CD-138 negative fractions and acellular fractions, including T, NK, and monocyte subsets using pre- and on-daratumumab treatment samples by flow cytometry.

V. Assess possible changes in CD38+ expression, as well as the co-receptor marker CD31, and possible correlation with response using pre- and on-daratumumab treatment samples by flow cytometry.

VI. Assess cytokine levels in the bone marrow acellular fraction. VII. Investigate CD38 cellular localization in multiple myeloma cells and extracellular vesicles from blood plasma.

VIII. Assess messenger ribonucleic acid (mRNA) expression in the PBMC, the bone marrow CD130-negative fraction, the T cell fraction, and multiple myeloma cells.

IX. If differences in CD38 expression are found, investigate epigenetic changes in CD38 mRNA expression.

OUTLINE

Patients undergo standard of care ASCT with a conditioning regimen of melphalan. Beginning 60-120 days after ASCT, patients receive daratumumab intravenously (IV) every week for 8 weeks, every 2 weeks for 16 weeks, and then every 4 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 18 months.

Details
Condition Plasma Cell Myeloma, Secondary Amyloidosis
Treatment laboratory biomarker analysis, melphalan, autologous hematopoietic stem cell transplantation, Daratumumab
Clinical Study IdentifierNCT03346135
SponsorCity of Hope Medical Center
Last Modified on28 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

All subjects must have the ability to understand and the willingness to sign a written informed consent
Histologically confirmed diagnosis of multiple myeloma; (patients with multiple myeloma with secondary amyloidosis are eligible)
Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-13 months of the first dose of initial therapy
Eastern Cooperative Oncology Group (ECOG) =< 2
Patients with planned standard of care ASCT using melphalan 200 mg/m^2; dose modifications in accordance with creatinine clearance levels are allowed per physician judgment
Adequate organ function for high dose chemotherapy and autologous stem cell transplant (as per institution standard operating procedure [SOP])
Adequate cell dose > 2.5 x 10^6 CD34+ cells/kg
Absolute neutrophil count (ANC) >= 1000/mm^3
Platelet count >= 75,000/mm^3; platelet transfusions to help patients meet eligibility criteria are not allowed within 7 days before study enrollment
Total bilirubin =< 1.5 x the upper limit of normal (ULN)
Aspartate aminotransferase (AST) =< 3 x ULN
Alanine aminotransferase (ALT) =< 3 x ULN
Calculated creatinine clearance >= 30 mL/min
Woman of childbearing potential must be practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected, or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods; condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization; true abstinence (when this is in line with the preferred and usual lifestyle of the subject) during and after the study (6 months after the last dose of daratumumab for women)
A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control, e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 6 months after receiving the last dose of study drug

Exclusion Criteria

Prior disease progression with daratumumab or other anti-CD38 antibody
History of organ or previous autologous/allogeneic stem cell transplantation
Any condition medical or psychosocial that in the opinion of the investigator would hinder compliance
Female patients who are lactating or have a positive pregnancy test during the screening period
Evidence of multiple myeloma (MM) disease progression any time prior to enrollment; progression from smoldering to active myeloma is not exclusionary
History of plasma cell leukemia or central nervous system (CNS) involvement
Major surgery within 14 days prior to start of study treatment
Infection requiring systemic antibiotic therapy within 14 days prior to the start of study treatment
Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment; Note: Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes) is acceptable
Vaccination with live attenuated vaccines within 4 weeks of first study agent administration
Subject is currently using or has used immunosuppressive medication within 14 days prior to the first dose of study treatment; the following are exceptions
Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection)
Chronic systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
Steroids as premedication for hypersensitivity reaction (e.g., infusion-related reactions, computed tomography [CT] scan premedication)
Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome
Subjects with uncontrolled, systematic infection should be excluded
(polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin
Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% predicted normal; Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 < 50%
changes), or primary amyloidosis
Subject has known moderate or severe persistent asthma within 2 years, or currently has uncontrolled asthma of any classification; (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study)
Subject has active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., Crohn's disease], diverticulitis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis, etc) within the past 3 years prior to the start of treatment; the following are exceptions
Subjects with vitiligo or alopecia
Subjects with hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement
Psoriasis not requiring systemic treatment
Subject has history of primary immunodeficiency
Subject is seropositive for human immunodeficiency virus (HIV-1)
Subject has known allergies, hypersensitivity, or intolerance to monoclonal antibodies
Active hepatitis A
or human proteins, or their excipients
Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]); subjects with resolved infection (I.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs] must be screened using real-time polymerase chain reaction [PCR] measurement of hepatitis B virus [HBV] deoxyribonucleic acid [DNA] levels; those who are PCR positive will be excluded); EXCEPTION: Subjects with serologic finding suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
Subject has any one of the following
Clinically significant abnormal electrocardiogram (ECG) finding at screening
Congestive heart failure (New York Heart Association class III or IV)
Myocardial infarction within 12 months prior to starting study treatment
Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
Basal cell carcinoma of the skin
Squamous cell carcinoma of the skin
Subject has prior history of malignancies, other than MM, unless the subject has been
Carcinoma in situ of the cervix
free of the disease for >= 5 years with the exception of the following
Carcinoma in situ of the breast
malignancies
Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis [TNM] clinical staging system) or prostate cancer that is curative
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Any other condition that would, in the opinion of the investigator's judgement
contraindicate the patient's participation in the clinical study due to safety
concerns with clinical study procedures
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note