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

NCT03356054 | Recruiting Phase 1 DMC

• 2 other identifiers: HO1362016-001211-21
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

DLBCL

Outcome Measures

Primary Outcomes (3)

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

  Phase I

  6 weeks

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

  Phase II

  9 weeks

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

  Phase II

  up to 12 weeks

Study Arms (1)

Brentuximab vedotin-R-DHAP

EXPERIMENTAL

Brentuximab vedotin added to R-DHAP

Combination Product: R-DHAP; Drug: Brentuximab Vedotin

Interventions

R-DHAP COMBINATION_PRODUCT

3 cycles q 3 weeks

Brentuximab vedotin-R-DHAP

Brentuximab Vedotin DRUG

3 cycles q 3 weeks added to R-DHAP

Also known as: Adcetris

Brentuximab vedotin-R-DHAP

Eligibility Criteria

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

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Stichting Hemato-Oncologie voor Volwassenen Nederland: lead

Study Sites (1)

NL-Rotterdam-ERASMUSMC

Rotterdam, Netherlands

RECRUITING

Related Links

• Website HOVON Foundation (sponsor)

MeSH Terms

Interventions

Brentuximab Vedotin

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• P.J. Lugtenburg, Dr.

  NL-Rotterdam-ErasmusMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

P.J. Lugtenburg, Dr.

CONTACT

+31 (0)10 7031672; p.lugtenburg@erasmusmc.nl

M. Minnema, Prof. dr.

CONTACT

m.c.minnema@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2017
• First Posted: November 29, 2017
• Study Start: March 5, 2018
• Primary Completion: January 1, 2023
• Study Completion (Estimated): February 1, 2027
• Last Updated: December 10, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)