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DLBCLPhase 1/2HOVON 136 NHLNCT03356054

Phase I-II Study in CD30 Positive Diffuse Large B-cell Lymphoma Patients Refractory to First Line Chemotherapy or in First Relapse

A Phase 1/2 study testing R-DHAP and Brentuximab Vedotin in people with DLBCL, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 1 site in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Patients with CD30 positive DLBCL, primary refractory or in first relapse after R-CHOP or R-CHOP-like therapy will receive brentuximab vedotin in combination with R-DHAP, followed in responsive patients by high dose chemotherapy and ASCT. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
DLBCL
What is being tested?
R-DHAP and Brentuximab Vedotin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
1 siteNetherlands
Study dates
5 Mar 2018to Feb 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • CD30 positive DLBCL, i.e. more than 1% of DLBCL cells CD30 positive(central pathology review results not required to enter patient into the study), according to the WHO classification 2008:
  • CD30 positive DLBCL, including EBV positive DLBCL
  • CD30 positive primary mediastinal B-cell lymphoma
  • Primary refractory to or in first relapse after first line therapy with R-CHOP or R-CHOP-like therapy
  • Relapse is defined as biopsy confirmed CD30 positive DLBCL after a complete response. The relapse must be histologically confirmed. In case a surgical biopsy is not possible, at least confirmation by FNA biopsy is required
  • Refractory disease is defined as:
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  • progressive disease during first line therapy, In this case biopsy confirmation of CD30 positive DLBCL is preferred but not required
  • stable disease after at least 3 cycles of first line therapy, In this case biopsy confirmation of CD30 positive DLBCL is preferred but not required
  • PR after at least 6 cycles of first line therapy, or in the case of stage I-II disease after at least 3 cycles of therapy and definitive involved field radiotherapy. In this case refractory disease must be histologically confirmed
  • Age ≥ 18 years (upper age limit for ASCT at the discretion of the participating center)
  • Measurable disease: on CT scan at least 1 lesion/node with a long axis of > 1.5 cm and at least one positive lesion on 18F-FDG PET scan
  • WHO performance status 0-2, status 3 only if disease related (see appendix C)
  • Adequate hepatic function: total bilirubin ≤ 1.5 times ULN (unless due to lymphoma involvement of the liver or a known history of Gilbert's syndrome as defined by > 80% unconjugated bilirubin) and ALAT/ASAT ≤ 3 times ULN (unless due to lymphoma involvement of the liver; in that case ALAT/ASAT may be elevated up to 5 times ULN)
  • Adequate renal function: GFR > 60 ml/min as estimated by the Cockroft\&Gault formula at rehydration: CrCL = (140-age [in years] x weight [kg] (x 0.85 for females) / (0.815 x serum creatinine [μmol/L])
  • Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5x109/L and platelet count ≥ 100 x 109/L, unless caused by diffuse bone marrow infiltration by the NHL
  • Hemoglobin must be ≥ 8 g/dL (5.0 mmol/L), transfusion is allowed
  • Eligible for high-dose chemotherapy and ASCT
  • Resolution of relevant toxicities from first-line therapy
  • Life expectancy of > 3 months with treatment
  • Negative pregnancy test at study entry, if applicable
  • Female patient is either post-menopausal for at least 1 year before screening visit or surgically sterile or if of childbearing potential, agrees to practice 2 effective methods of contraception, at the same time, or agrees to completely abstain from heterosexual intercourse, from the time of signing the informed consent through 12 months after the last dose of study drug
  • Male patients, even if surgically sterilized, (i.e. status post vasectomy) agree to practice effective barrier contraception, or agrees to completely abstain from heterosexual intercourse, during the entire study period and through 12 months after the last dose of study drug
  • Written informed consent
  • Patient is capable of giving informed consent

Who cannot join

  • Peripheral sensory or motor neuropathy grade ≥ 2
  • Known cerebral or meningeal disease (NHL or any other etiology), including signs and symptoms of progressive multifocal leukoencephalopathy (PML)
  • Symptomatic neurological disease compromising normal activities of daily living or requiring medications
  • Transformed lymphoma
  • DLBCL after organ transplantation
  • Immunodeficiency-associated B-cell lymphoproliferative disease
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  • Use of other investigational agents within at least 5 half-lives of the most recent agent used prior to study entry
  • Treatment with myelosuppressive chemotherapy or biological therapy ≤ 4 weeks before study entry
  • Female patients who are breast feeding
  • History of another malignancy less than 3 years before study inclusion, or previously diagnosed with another malignancy and have evidence of residual disease, with the exception of non-melanoma skin cancer, completely resected melanoma TNMpT1 and carcinoma in situ of the uterine cervix
  • Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin
  • Active hepatitis B or C infection as defined by positive serology and transaminitis. Non-active hepatitis B carriers or anti-HBc positive patients may be included if protected with lamuvidine or entecavir (see 9.4)
  • HIV positivity
  • Radiation therapy within 8 weeks prior to start of protocol treatment. Emergency radiation therapy is allowed, as long as measurable disease (at non-irradiated sites) persists
  • Patients with a serious psychiatric disorder that could, in the investigator's opinion, potentially interfere with the completion of treatment according to protocol
  • Major organ dysfunction, unless NHL-related
  • Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study such as:
  • Known history of symptomatic congestive heart failure (NYHA III, IV, appendix E), myocardial infarction ≤ 6 months prior to first study drug
  • Evidence of current serious uncontrolled cardiac arrhythmia, angina pectoris, electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <45%
  • Severely impaired pulmonary function as defined as spirometry and DLCO (diffusing capacity of the lung for carbon monoxide) that is 50% or less of the normal predicted value and/or O2 saturation that is 90% or less at rest on room air
  • Thyroid abnormalities when thyroid function cannot be maintained in the normal range by medication
  • Current participation in another clinical trial interfering with this trial
  • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Claustrophobia to the extent that PET-CT is impossible

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

P.J. Lugtenburg, Dr. contact

+31 (0)10 7031672

p.lugtenburg@erasmusmc.nl

M. Minnema, Prof. dr. contact

m.c.minnema@umcutrecht.nl

Netherlands1 site, 1 recruiting

  • NL-Rotterdam-ERASMUSMC

    Rotterdam

    Recruiting

Other trials in Netherlands

About this study

Official title: Phase I-II Study Combining Brentuximab Vedotin With Second Line Salvage Chemotherapy (R-DHAP) in CD30 Positive Diffuse Large B-cell Lymphoma Patients Refractory to First Line Chemotherapy or in First Relapse Who Are Eligible for High Dose Treatment Followed by Autologous Stem Cell Transplantation

Patients with CD30 positive DLBCL, primary refractory or in first relapse after R-CHOP or R-CHOP-like therapy will receive brentuximab vedotin in combination with R-DHAP, followed in responsive patients by high dose chemotherapy and ASCT.

Read the detailed description

Patients with primary refractory or relapse diffuse large B cell lymphoma (DLBCL) after R-CHOP have a dismal prognosis. Only 25% long term survivors are observed after salvage with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). CD30 expression is observed in 30% of refractory/relapse DLBCL.

Monotherapy with brentuximab vedotin is effective in relapse CD30 positive DLBCL. The addition of brentuximab vedotin to R-DHAP might improve the prognosis of these patients.

Treatment will consist of 3 cycles of brentuximab-vedotin in combination with R-DHAP. During the phase I part the recommended dose level for this combination will be established. Cycles will be given every 3 weeks.

Responsive patients will be treated with BEAM followed by ASCT. Total treatment duration is approximately 16 weeks.

Subsequently patients will be followed until 5 years after registration.

Conditions
DLBCL
Being tested
R-DHAP, Brentuximab Vedotin

What participants receive

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

  • R-DHAPCombination product

    3 cycles q 3 weeks

  • Brentuximab VedotinDrug

    Also called Adcetris

    3 cycles q 3 weeks added to R-DHAP

Study groups in NCT03356054
Study groupRoleWhat they receive
Brentuximab vedotin-R-DHAPExperimentalBrentuximab vedotin added to R-DHAP
Receives: Combination Product: R-DHAP; Drug: Brentuximab Vedotin

What is being measured

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

  1. The rate of patients with serious toxicity during cycle 1-2 of the combination brentuximab vedotin-R-DHAP

    Phase I

    Measured: 6 weeks

  2. Metabolic CR rate (PET-diagnostic CT) after the third cycle of brentuximab vedotin-R-DHAP salvage therapy

    Phase II

    Measured: 9 weeks

  3. Rate of CTCAE grade 3/4 non-hematological toxicity, including neurotoxicity after each cycle of brentuximab vedotin-R-DHAP

    Phase II

    Measured: up to 12 weeks

Timeline

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

  1. First posted29 Nov 2017
  2. Study start5 Mar 2018
  3. Primary completionJan 2023 (estimated)
  4. Study completionFeb 2027 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03356054
Sponsor's protocol ID
HO136
Other IDs
2016-001211-21, 2016
Acronym
HOVON 136 NHL
Status last verified
Dec 2020
First submitted
15 Nov 2017
Last updated
10 Dec 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing R-DHAP and Brentuximab Vedotin in people with DLBCL, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 1 site in Netherlands.

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 24 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 10 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact P.J. Lugtenburg, Dr. (+31 (0)10 7031672, p.lugtenburg@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The rate of patients with serious toxicity during cycle 1-2 of the combination brentuximab vedotin-R-DHAP (time frame: 6 weeks). The study lists 3 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 NCT03356054.

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 10 Dec 2020.

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