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Plasma Cell LeukemiaPhase 1NCT02504359

Combination Chemotherapy and Donor Stem Cell Transplant Followed by Ixazomib Citrate Maintenance Therapy in Treating Patients With Relapsed High-Risk Multiple Myeloma

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Carmustine and Cytarabine in people with Plasma Cell Leukemia and Recurrent Plasma Cell Myeloma, run by OHSU Knight Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase Ib trial studies the side effects of combination chemotherapy and donor stem cell transplant followed by ixazomib citrate maintenance therapy in treating patients with multiple myeloma that has returned after a period of improvement and is likely to recur (come back), or spread. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Carmustine and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
2 sitesUnited States
Study dates
20 Jul 2015to 9 Sep 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Relapsed multiple myeloma in patients that have been treated previously with autologous hematopoietic stem cell transplantation (auto-HCT), bortezomib and an immunomodulatory agent, AND with at least one of the following high-risk criteria
  • High-risk multiple myeloma defined by cytogenetic or fluorescence in situ hybridization (FISH) detection of any one or more of the following:
  • Deletion 17p
  • Translocation t(4;14)
  • Translocation t(14;16)
  • Translocation t(14;20)
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  • Chromosome 1q gain
  • Chromosome 1p deletion
  • Deletion 13q by conventional karyotyping (FISH only not acceptable)
  • Hypodiploidy
  • High-risk gene expression profiling (GEP) at the time of relapse
  • Beta-2 (B2) microglobulin > 5.5 mg
  • Plasmablastic morphology (> 2%)
  • Relapsed plasma cell leukemia
  • Chemo-sensitive disease; patients with relapsed plasma cell leukemia may have received systemic therapy including an autologous transplant but it is not required; patients with relapsed multiple myeloma (MM) must have received prior systemic therapy including an autologous transplant; patient must be in at least a PR at the time of transplant; early relapse from complete response will be allowed
  • Measurable disease at the time of relapse, defined as a monoclonal immunoglobulin spike on serum electrophoresis of >= 1 gm/dL (immunoglobulin [IG]G) or >= 0.5 gm/dL (IGA) and/or urine monoclonal immunoglobulin spike of > 200 mg/24 hours and/ or involved free light chain (FLC) level >= 10 mg/dl and the serum FLC ratio is abnormal
  • Non-secretors must have measurable disease such as plasmacytomas, or positron emission tomography (PET) avid lytic lesions or bone marrow plasmacytosis >= 30% at the time of relapse to be eligible
  • The patient must have an available sibling or matched unrelated donor with at least a 7/8 human leukocyte antigen (HLA) match
  • Creatinine =< 2.0 mg/dL
  • Ejection fraction >= 45%
  • Diffusing capacity of the lungs for carbon monoxide (DLCO) >= 50%
  • Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) >= 50% predicted
  • Both men and women and members of all races and ethnic groups will be included
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
  • Willing to use adequate contraception for the duration of time on the study and for 90 days after the last therapy
  • Female patients must meet one of the following:
  • Postmenopausal for at least 1 year before the screening visit, OR
  • Surgically sterile, OR
  • If they are of childbearing potential:
  • Agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
  • DONOR: HLA genotypically identical sibling matched relative
  • DONOR: HLA matched unrelated donor according to Standard Practice HLA matching criteria:
  • Matched HLA-A, -B, -C, and -DRB1 alleles by high resolution typing
  • Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing

Who cannot join

  • Previous allogeneic stem cell transplant
  • POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [protein] and skin changes)
  • Bilirubin > 1.5 x the upper limit of normal
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 x the upper limit of normal
  • Patients with >= grade III or grade II with pain peripheral neuropathy (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 4.03 criteria)
  • Receiving steroids > the equivalent of 10 mg prednisone daily for other medical conditions, e.g., asthma, systemic lupus erythematosus, rheumatoid arthritis
Show all 29Show fewer
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
  • Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
  • Second malignancy requiring concurrent treatment or those with non-hematological malignancies (except non-melanoma skin cancers); cancer treated with curative intent < 5 years previously will not be allowed unless approved by the protocol chair; cancer treated with curative intent > 5 years previously is allowed
  • Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
  • Radiotherapy within 14 days before enrollment; if the involved field is limited to a single site, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
  • Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
  • Female patients who are lactating or have a positive serum pregnancy test during the screening period
  • Failure to have fully recovered (i.e., =< grade 1 toxicity) from the reversible effects of prior chemotherapy
  • Major surgery within 14 days before enrollment
  • Central nervous system involvement
  • Participation in other clinical treatment trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial
  • DONOR: Identical twin
  • DONOR: Donors unwilling to donate PBSC
  • DONOR: Pregnancy
  • DONOR: Infection with HIV
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to filgrastim (G-CSF)
  • DONOR: Current serious systemic illness
  • DONOR: Failure to meet institutional criteria for stem cell donation
  • DONOR: Patient and donor pairs must not be homozygous at mismatched allele

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Feasibility Study of Myeloablative BEAM Allogeneic Transplantation Followed by Oral Ixazomib Maintenance Therapy in Patients With Relapsed High-Risk Multiple Myeloma

This phase Ib trial studies the side effects of combination chemotherapy and donor stem cell transplant followed by ixazomib citrate maintenance therapy in treating patients with multiple myeloma that has returned after a period of improvement and is likely to recur (come back), or spread. Giving chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving ixazomib citrate after the transplant may improve the overall treatment outcome without causing additional toxicities.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Safety of BEAM (carmustine, cytarabine, etoposide, melphalan) allogeneic transplant within 100 days, defined as the day 100 transplant related mortality (TRM).

II. Safety of oral ixazomib maintenance therapy from day 100 post allogeneic transplant up to 2 years, defined by the incidence of grade III-IV acute (or overlap) graft-versus-host disease (GvHD) and grade III-IV ixazomib related toxicity.

OUTLINE:

BEAM CONDITIONING REGIMEN: Patients receive carmustine on day -6, cytarabine and etoposide on days -5 to -2, and melphalan on day -1.

PERIPHERAL BLOOD STEM CELL TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus intravenously (IV) or orally (PO) on days -2 to at least 6 months with a taper as early as 3 months post-transplant and methotrexate IV on days 1, 3, 6, and 11.

MAINTENANCE THERAPY: Beginning between days 100 and 180 post-transplant, patients receive ixazomib PO on days 1 and 14 or days 1, 8, and 15 if the principal investigator deems it medically important. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days through 4 months post last dose of ixazomib.

Being tested
Allogeneic Hematopoietic Stem Cell Transplantation, Carmustine, Cytarabine, Etoposide, Ixazomib Citrate
Keywords
BEAM, allogeneic, myeloma, ixazomib, transplant, plasma cell leukemia
Medical subject headings
Leukemia, Plasma Cell, Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

    Undergo allogeneic peripheral blood stem cell transplantation

  • CarmustineDrug

    Also called BCNU, Becenum, Becenun, BiCNU

    Given BEAM chemotherapy

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given BEAM chemotherapy

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given BEAM chemotherapy

  • Ixazomib CitrateDrug

    Also called MLN-9708, MLN9708, Ninlaro

    Given PO

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given BEAM chemotherapy

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, peripheral stem cell support

    Undergo allogeneic peripheral blood stem cell transplantation

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV or PO

Study groups in NCT02504359
Study groupRoleWhat they receive
Treatment (BEAM allogeneic transplant, ixazomib)ExperimentalBEAM CONDITIONING REGIMEN: Patients receive carmustine on day -6, cytarabine and etoposide on days -5 to -2, and melphalan on day -1. PERIPHERAL BLOOD STEM CELL TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO on days -2 to at least 6 months with a taper as early as 3 months post-transplant and methotrexate IV on days 1, 3, 6, and 11. MAINTENANCE THERAPY: Beginning between days 100 and 180 post-transplant, patients receive ixazomib PO on days 1 and 14 or days 1, 8, and 15 if the principal investigator deems it medically important. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Drug: Ixazomib Citrate; Drug: Melphalan; Drug: Methotrexate; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Quality-of-Life Assessment; Drug: Tacrolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Transplant related mortality (TRM)

    Time to event analysis will be conducted to estimate day 100 TRM and its confidence interval among those who receive carmustine, cytarabine, etoposide, melphalan (BEAM) allogeneic transplantation.

    Measured: At day 100

  2. Incidence of grade III-IV acute (or overlap) graft versus host disease (GvHD) and ixazomib related grade III-IV toxicity

    Time to event analysis will be conducted to estimate the incidence of acute (or overlap) GvHD and grade III-IV treatment related toxicity among those who receive ixazomib maintenance therapy, accounting for possible competing risks and events. All treatment related toxicity will be tabulated and summarized by severity and major organ categories defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2015 (estimated)
  2. Study start20 Jul 2015
  3. Primary completion9 Sep 2020
  4. Study completion9 Sep 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02504359
Sponsor's protocol ID
IRB00011097
Other IDs
NCI-2015-01065, HEM-14099-LM, IRB00011097
Status last verified
Nov 2020
First submitted
20 Jul 2015
Last updated
23 Nov 2020
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Carmustine and Cytarabine in people with Plasma Cell Leukemia and Recurrent Plasma Cell Myeloma, run by OHSU Knight Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 41 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Transplant related mortality (TRM) (time frame: At day 100). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02504359.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2020.

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