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NCT01780662

Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma

Completed Phase 1, PHASE2 Results posted Last updated 28 October 2021
What this trial tests

Phase 1, PHASE2 trial testing Brentuximab Vedotin in Recurrent Adult Hodgkin Lymphoma in 46 participants. Completed in 30 September 2021.

Timeline
31 January 2013
Primary endpoint
30 September 2017
30 September 2021

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment46
Start date31 January 2013
Primary completion30 September 2017
Estimated completion30 September 2021
Sites116 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 13 Months to 30, any sex, with Recurrent Adult Hodgkin Lymphoma or Recurrent Childhood Hodgkin Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Tolerated Dose (MTD) for Brentuximab Vedotin Primary · During cycle 1 of protocol therapy (21 days)

MTD was determined as the maximum dose at which fewer than one-third of patients experience Dose Limiting Toxicities (DLT) as assessed by National Cancer Institute (NCI) CTCAE v 4.0 during Cycle 1 of therapy. Gemcitabine was administered on days 1 and 8 of a 21 day cycle at a fixed dose. Brentuximab vedotin was investigated at a starting dose of 1.4 mg/kg administered on day 1 and escalated if tolerated.

GroupValue95% CI
Treatment (Brentuximab Vedotin, Gemcitabine Hydrochloride)1.8
Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Primary · 13 months from first dose

The number of eligible patients assigned to receive brentuximab vedotin in combination with gemcitabine that experienced CTC Version 4, grade 3 or higher adverse events during Phase 1 and Phase 2.

Abdominal pain
GroupValue95% CI
Dose 1.4mg/kg (Phase I)0
Dose 1.8mg/kg (Phase I + Phase II)1
Adrenal insufficiency
GroupValue95% CI
Dose 1.4mg/kg (Phase I)0
Dose 1.8mg/kg (Phase I + Phase II)1
Alanine aminotransferase increased
GroupValue95% CI
Dose 1.4mg/kg (Phase I)1
Dose 1.8mg/kg (Phase I + Phase II)13
Anemia
GroupValue95% CI
Dose 1.4mg/kg (Phase I)1
Dose 1.8mg/kg (Phase I + Phase II)4
Anorexia
GroupValue95% CI
Dose 1.4mg/kg (Phase I)0
Dose 1.8mg/kg (Phase I + Phase II)1
Aspartate aminotransferase increased
GroupValue95% CI
Dose 1.4mg/kg (Phase I)1
Dose 1.8mg/kg (Phase I + Phase II)10
Dehydration
GroupValue95% CI
Dose 1.4mg/kg (Phase I)0
Dose 1.8mg/kg (Phase I + Phase II)1
Dental caries
GroupValue95% CI
Dose 1.4mg/kg (Phase I)0
Dose 1.8mg/kg (Phase I + Phase II)1
The Number of Patients With Relapsed or Refractory HL Who Achieved Complete Response (CR) Primary · After 4 cycles (21 days per cycle) of protocol therapy

The number of patients who experienced complete Response (CR) within the first four cycles. By modern response criteria, those with partial response (PR) or stable disease with all target lesions with Deauville scores \<=3 after cycle 4 are also considered as CR. Patients were assessed after treatment with four cycles of gemcitabine with brentuximab vedotin. CR was only reported for Dose level 2 across both phases of study.

GroupValue95% CI
Treatment (Brentuximab Vedotin, Gemcitabine Hydrochloride)28
The Number of Patients Who Had Disease Response Assessed by Deauville Scales Among Those in Phase I With Dose Level 2. Secondary · Up to 13 months from first dose

The Deauville five-point scale was used to assess the number of participants with complete response (CR) and partial response (PR). A lower score indicates a better outcome. Scores of 1-3 represent CR and 4-5 represent PR.

GroupValue95% CI
Treatment (Brentuximab Vedotin, Gemcitabine Hydrochloride)8
Percentage of Patients Who Achieved Overall Response (OR) as Measured by Complete Response (CR) and Partial Response (PR) Secondary · After 4 cycles (21 days per cycle) of protocol therapy

The percentage of patients who experienced complete Response (CR) within the first four cycles.By modern response criteria, those with partial response (PR) or stable disease with all target lesions with Deauville scores \<=3 after cycle 4 are also considered as CR. Patients were assessed after treatment with four cycles of gemcitabine with brentuximab vedotin. CR was only reported for Dose level 2 across both phases of study.

GroupValue95% CI
Treatment (Brentuximab Vedotin, Gemcitabine Hydrochloride)7458 – 86
The Number of Patients Who Had Successful Peripheral Blood Stem Cell (PBSC) Collection Secondary · From 1 to 5 cycles

Successful PBSC collection was defined as a collection of more than 2x10\^6 CD34 positive cells.

GroupValue95% CI
Treatment (Brentuximab Vedotin, Gemcitabine Hydrochloride)24
Plasma Level of Thymus and Activation-Regulated Chemokine (TARC) Secondary · From baseline to time prior to cycle 2

Limit to 41 evaluable patients who received dose 1.8 mg/kg

Baseline
GroupValue95% CI
Dose 1.8mg/kg5700389 – 18,667
Prior to Cycle 2
GroupValue95% CI
Dose 1.8mg/kg6686 – 9,718
Number of Patients With FcyRIIIa-158 V/F (Valine/Phenylalanine) Polymorphism Secondary · From the end of first dose to the end of last dose (Up to 13 Months)

Among patients who received 1.8mg/kg dose, the frequency of the FcγRIIIa-158 V/F polymorphism are described.

Homozygous FF- Phenylalanine
GroupValue95% CI
Dose 1.8mg/kg22
Heterozygous FV- Valine/Phenylalanine
GroupValue95% CI
Dose 1.8mg/kg14
Homozygous VV- Valine
GroupValue95% CI
Dose 1.8mg/kg5

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose up to 13 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose1.4mg/kg
Serious: 3/3 (100%)
Deaths: 2/3
Dose 1.8mg/kg
Serious: 37/42 (88%)
Deaths: 2/42

Serious adverse events (31 terms)

ReactionSystemDose1.4mg/kgDose 1.8mg/kg
Neutrophil count decreasedInvestigations
White blood cell decreasedInvestigations
Alanine aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
Aspartate aminotransferase increasedInvestigations
Lymphocyte count decreasedInvestigations
AnemiaBlood and lymphatic system disorders
HypotensionVascular disorders
DiarrheaGastrointestinal disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Febrile neutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Lung infectionInfections and infestations
HypophosphatemiaMetabolism and nutrition disorders
Hemolytic uremic syndromeBlood and lymphatic system disorders
Pericardial effusionCardiac disorders
Adrenal insufficiencyEndocrine disorders
Abdominal painGastrointestinal disorders
Dental cariesGastrointestinal disorders
Non-cardiac chest painGeneral disorders
Infections and infestations - Other- SpecifyInfections and infestations
Skin infectionInfections and infestations
Urinary tract infectionInfections and infestations
GGT increasedInvestigations
Investigations - Other- SpecifyInvestigations
Other adverse events (100 terms — click to expand)

ReactionSystemDose1.4mg/kgDose 1.8mg/kg
Rash maculo-papularSkin and subcutaneous tissue disorders
Aspartate aminotransferase increasedInvestigations
NauseaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
VomitingGastrointestinal disorders
FatigueGeneral disorders
FeverGeneral disorders
Alkaline phosphatase increasedInvestigations
HeadacheNervous system disorders
AnemiaBlood and lymphatic system disorders
PruritusSkin and subcutaneous tissue disorders
Platelet count decreasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
Lymphocyte count decreasedInvestigations
White blood cell decreasedInvestigations
HypocalcemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
HypoalbuminemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
ParesthesiaNervous system disorders
Peripheral motor neuropathyNervous system disorders
Peripheral sensory neuropathyNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Sore throatRespiratory, thoracic and mediastinal disorders
UrticariaSkin and subcutaneous tissue disorders
Sinus tachycardiaCardiac disorders
ConstipationGastrointestinal disorders
ChillsGeneral disorders
MalaiseGeneral disorders
Enterocolitis infectiousInfections and infestations
Carbon monoxide diffusing capacity decreasedInvestigations
Creatinine increasedInvestigations
Investigations - Other- SpecifyInvestigations
Weight gainInvestigations
AnorexiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Neutrophil count decreased, White blood cell decreased, Alanine aminotransferase increased, Platelet count decreased, Aspartate aminotransferase increased, Lymphocyte count decreased, Anemia, Hypotension.

Data from ClinicalTrials.gov NCT01780662 adverse events section.

Sponsor's own description

This phase I/II trial studies the side effects and the best dose of brentuximab vedotin when given together with gemcitabine hydrochloride and to see how well they work in treating younger patients with Hodgkin lymphoma that has returned or does not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may find cancer cells and help kill them. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin together with gemcitabine hydrochloride may kill more cancer cells.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Pediatric Cancer Immunotherapy: Opportunities and Challenges.
    Wedekind MF, Denton NL, Chen CY, Cripe TP. · · 2018 · cited 78× · PMID 29948928 · DOI 10.1007/s40272-018-0297-x
  2. Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): a Children's Oncology Group, multicentre single-arm, phase 1-2 trial.
    Cole PD, McCarten KM, Pei Q, Spira M, et al · · 2018 · cited 59× · PMID 30122620 · DOI 10.1016/s1470-2045(18)30426-1
  3. Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update.
    Bayraktar E, Bayraktar R, Oztatlici H, Lopez-Berestein G, et al · · 2023 · cited 51× · PMID 37104009 · DOI 10.3390/ncrna9020027
  4. Advances in paediatric cancer treatment.
    Saletta F, Seng MS, Lau LM. · · 2014 · cited 50× · PMID 26835334 · DOI 10.3978/j.issn.2224-4336.2014.02.01
  5. Recent Advances of Cell-Cycle Inhibitor Therapies for Pediatric Cancer.
    Mills CC, Kolb EA, Sampson VB. · · 2017 · cited 48× · PMID 29097609 · DOI 10.1158/0008-5472.can-17-2066
  6. MicroRNAs in cancer therapeutics: "from the bench to the bedside".
    Monroig-Bosque Pdel C, Rivera CA, Calin GA, Calin GA. · · 2015 · cited 34× · PMID 26372796 · DOI 10.1517/14712598.2015.1074999
  7. Pediatric Hodgkin lymphoma: biomarkers, drugs, and clinical trials for translational science and medicine.
    Nagpal P, Akl MR, Ayoub NM, Tomiyama T, et al · · 2016 · cited 30× · PMID 27563824 · DOI 10.18632/oncotarget.11509
  8. Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies.
    Kyriakidis I, Vasileiou E, Rossig C, Roilides E, et al · · 2021 · cited 24× · PMID 33807678 · DOI 10.3390/jof7030186

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01780662.

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